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129 results on '"Carmosino, M."'

4. Lovastatin-induced cholesterol depletion affects both apical sorting and endocytosis of aquaporin-2 in renal cells

Author

Procino, G., Barbieri, C., Carmosino, M., Rizzo, F., Valenti, G., and Svelto, M.

Subjects
Biological sciences
Abstract

Vasopressin causes the redistribution of the water channel aquaporin-2 (AQP2) from cytoplasmic storage vesicles to the apical plasma membrane of collecting duct principal cells, leading to urine concentration. The molecular mechanisms regulating the selective apical sorting of AQP2 are only partially uncovered. In this work, we investigate whether AQP2 sorting/trafficking is regulated by its association with membrane rafts. In both MCD4 cells and rat kidney, AQP2 preferentially associated with Lubrol WX-insoluble membranes regardless of its presence in the storage compartment or at the apical membrane. Block-andrelease experiments indicate that 1) AQP2 associates with detergent-resistant membranes early in the biosynthetic pathway; 2) strong cholesterol depletion delays the exit of AQP2 from the trans-Golgi network. Interestingly, mild cholesterol depletion promoted a dramatic accumulation of AQP2 at the apical plasma membrane in MCD4 cells in the absence of forskolin stimulation. An internalization assay showed that AQP2 endocytosis was clearly reduced under this experimental condition. Taken together, these data suggest that association with membrane rafts may regulate both AQP2 apical sorting and endocytosis. membrane rafts doi: 10.1152/ajprenal.00359.2009

Published
2010

8. New insights on the functional role of URG7 in the cellular response to ER stress

Author

Armentano MF, Caterino M, Miglionico R, Ostuni A, Pace MC1, Cozzolino Flora, Monti M, Milella L, Carmosino M, Pucci P, Bisaccia F., Armentano, Mf, Caterino, M, Miglionico, R, Ostuni, A, Pace, Mc1, Cozzolino, Flora, Monti, M, Milella, L, Carmosino, M, Pucci, P, and Bisaccia, F.

Subjects
URG7, ER stress, UPR, PI3K/AKT, apoptosis
Abstract

BACKGROUND INFORMATION: Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is upregulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signaling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. RESULTS: To shed light on URG7 activity, we first analyzed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localization in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers toward survival outcomes, upregulating GRP78 protein and downregulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing caspase 3 activation. CONCLUSIONS: All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. SIGNIFICANCE: This is the first characterization of URG7 activity under ER stress conditions. The results presented here will help to hypothesize new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. This article is protected by copyright. All rights reserved.

Published
2018

9. ABCC6 knockdown in HepG2 cells induces a senescent-like cell phenotype. Cellular and

Author

Miglionico R, Ostuni A, Armentano MF1, Milella L, Crescenzi E, Carmosino M, and Bisaccia F.

Subjects
ABCC6, Cell cycle, Reductive stress, Senescence
Abstract

BACKGROUND: Pseudoxanthoma elasticum (PXE) is characterized by progressive ectopic mineralization of elastic fibers in dermal, ocular and vascular tissues. No effective treatment exists. It is caused by inactivating mutations in the gene encoding for the ATP-binding cassette, sub-family C member 6 transporter (ABCC6), which is mainly expressed in the liver. The ABCC6 substrate (s) and the PXE pathomechanism remain unknown. Recent studies have shown that overexpression of ABCC6 in HEK293 cells results in efflux of ATP, which is rapidly converted into nucleoside monophosphates and pyrophosphate (PPi). Since the latter inhibits mineralization, it was proposed that the absence of circulating PPi in PXE patients results in the characteristic ectopic mineralization. These studies also demonstrated that the presence of ABCC6 modifies cell secretory activity and suggested that ABCC6 can change the cell phenotype. METHODS: Stable ABCC6 knockdown HepG2 clones were generated using small hairpin RNA (shRNA) technology. The intracellular glutathione and ROS levels were determined. Experiments using cell cycle analysis, real-time PCR and western blot were performed on genes involved in the senescence phenotype. RESULTS: To shed light on the physiological role of ABCC6, we focused on the phenotype of HepG2 cells that lack ABCC6 activity. Interestingly, we found that ABCC6 knockdown HepG2 cells show: 1) intracellular reductive stress; 2) cell cycle arrest in G1 phase; 3) upregulation of p21Cip p53 independent; and 4) downregulation of lamin A/C. CONCLUSIONS: These findings show that the absence of ABCC6 profoundly changes the HepG2 phenotype, suggesting that the PXE syndrome is a complex metabolic disease that is not exclusively related to the absence of pyrophosphate in the bloodstream.

Published
2017

13. Martian fluvial conglomerates at gale crater

Author

Williams, R. M. E., Grotzinger, J. P., Dietrich, W. E., Gupta, S., Sumner, D. Y., Wiens, R. C., Mangold, N., Malin, M. C., Edgett, K. S., Maurice, S., Forni, O., Gasnault, O., Ollila, A., Newsom, H. E., Dromart, G., Palucis, M. C., Yingst, R. A., Anderson, R. B., Herkenhoff, K. E., Le Mouelic, S., Goetz, W., Madsen, M. B., Koefoed, A., Jensen, J. K., Bridges, J. C., Schwenzer, S. P., Lewis, K. W., Stack, K. M., Rubin, D., Kah, L. C., Bell, J. F., Farmer, J. D., Sullivan, R., Van Beek, T., Blaney, D. L., Pariser, O., Deen, R. G., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Edgar, L., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sobron Sanchez, P., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Aparicio, C. A., Caride Rodriguez, J., Carrasco Blazquez, I., Gomez Gomez, F., Elvira, J. G., Hettrich, S., Lepinette Malvitte, A., Marin Jimenez, M., Frias, J. M., Soler, J. M., Torres, F. J. M., Molina Jurado, A., Sotomayor, L. M., Munoz Caro, G., Navarro Lopez, S., Gonzalez, V. P., Garcia, J. P., Rodriguez Manfredi, J. A., Planello, J. J. R., Alejandra Sans Fuentes, S., Sebastian Martinez, E., Torres Redondo, J., O'Callaghan, R. U., Zorzano Mier, M.-P., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Squyres, S., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., Uston, C. d., Lasue, J., Lee, Q.-M., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Robert, F., Sautter, V., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Teinturier, S., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Conrad, P., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Harpold, D., Mahaffy, P., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Trainer, M., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., de la Torre Juarez, M., Vasavada, A. R., Webster, C. R., Yen, A., Archer, P. D., Cucinotta, F., Jones, J. H., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Leshin, L., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Blanco Avalos, J. J., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Gonzalez, R. N., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Kortmann, O., Williams, A., Lugmair, G., Wilson, M. A., Jakosky, B., Zunic, T. B., Frydenvang, J., Kinch, K., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Owen, T., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mellin, R. M., Schweingruber, R. W., McConnochie, T., Benna, M., Franz, H., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Atreya, S., Elliott, H., Halleaux, D., Renno, N., Wong, M., Pepin, R., Elliott, B., Spray, J., Thompson, L., Gordon, S., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, Petrology, GeoRessources, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
MSL Mars Gale Crater Fluvial Activity, Martian, Multidisciplinary, 010504 meteorology & atmospheric sciences, Outcrop, Curiosity rover, Geochemistry, Mars, Sediment, Fluvial, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars Exploration Program, 01 natural sciences, Abrasion (geology), martian fluvial conglomerates, 13. Climate action, Rocknest, 0103 physical sciences, MSL, Sedimentary rock, 010303 astronomy & astrophysics, Geology, 0105 earth and related environmental sciences
Abstract

Going to Mars The Mars Science Laboratory spacecraft containing the Curiosity rover, was launched from Earth in November 2011 and arrived at Gale crater on Mars in August 2012. Zeitlin et al. (p. 1080 ) report measurements of the energetic particle radiation environment inside the spacecraft during its cruise to Mars, confirming the hazard likely to be posed by this radiation to astronauts on a future potential trip to Mars. Williams et al. (p. 1068 , see the Perspective by Jerolmack ) report the detection of sedimentary conglomerates (pebbles mixed with sand and turned to rock) at Gale crater. The rounding of the rocks suggests abrasion of the pebbles as they were transported by flowing water several kilometers or more from their source.

Published
2013
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14. Abundance and isotopic composition of gases in the martian atmosphere from the Curiosity rover

Author

Mahaffy, P. R., Webster, C. R., Atreya, S. K., Franz, H., Wong, M., Conrad, P. G., Harpold, D., Jones, J. J., Leshin, L. A., Manning, H., Owen, T., Pepin, R. O., Squyres, S., Trainer, M., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Grotzinger, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stack, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Fairen, A., Hayes, A., Joseph, J., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Maurice, S., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Dromart, G., Robert, F., Sautter, V., Le Mouelic, S., Mangold, N., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Teinturier, S., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Wiens, R. C., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A. R., Yen, A., Archer, P. D., Cucinotta, F., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Navarro-Gonzalez, R., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Sumner, D. Y., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Elliott, H., Halleaux, D., Renno, N., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), MSL Science Team, NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
010504 meteorology & atmospheric sciences, Curiosity rover, chemistry.chemical_element, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars, MSL Mars Atmosphere Isotopis Composition, martian atmosphere, 01 natural sciences, Astrobiology, Isotopic signature, chemistry.chemical_compound, 0103 physical sciences, MSL, 010303 astronomy & astrophysics, 0105 earth and related environmental sciences, Martian, Multidisciplinary, δ13C, Atmosphere of Mars, Nitrogen, chemistry, 13. Climate action, Sample Analysis at Mars, Carbon dioxide, Environmental science, Carbon monoxide
Abstract

Mars' Atmosphere from Curiosity The Sample Analysis at Mars (SAM) instrument on the Curiosity rover that landed on Mars in August last year is designed to study the chemical and isotopic composition of the martian atmosphere. Mahaffy et al. (p. 263 ) present volume-mixing ratios of Mars' five major atmospheric constituents (CO 2 , Ar, N 2 , O 2 , and CO) and isotope measurements of 40 Ar/ 36 Ar and C and O in CO 2 , based on data from one of SAM's instruments, obtained between 31 August and 21 November 2012. Webster et al. (p. 260 ) used data from another of SAM's instruments obtained around the same period to determine isotope ratios of H, C, and O in atmospheric CO 2 and H 2 O. Agreement between the isotopic ratios measured by SAM with those of martian meteorites, measured in laboratories on Earth, confirms the origin of these meteorites and implies that the current atmospheric reservoirs of CO 2 and H 2 O were largely established after the period of early atmospheric loss some 4 billion years ago.

Published
2013
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15. Curiosity at Gale Crater, Mars: Characterization and analysis of the rocknest sand shadow

Author

Blake, D. F., Morris, R. V., Kocurek, G., Morrison, S. M., Downs, R. T., Bish, D., Ming, D. W., Edgett, K. S., Rubin, D., Goetz, W., Madsen, M. B., Sullivan, R., Gellert, R., Campbell, I., Treiman, A. H., McLennan, S. M., Yen, A. S., Grotzinger, J., Vaniman, D. T., Chipera, S. J., Achilles, C. N., Rampe, E. B., Sumner, D., Meslin, P.- Y., Maurice, S., Forni, O., Gasnault, O., Fisk, M., Schmidt, M., Mahaffy, P., Leshin, L. A., Glavin, D., Steele, A., Freissinet, C., Navarro-Gonzalez, R., Yingst, R. A., Kah, L. C., Bridges, N., Lewis, K. W., Bristow, T. F., Farmer, J. D., Crisp, J. A., Stolper, E. M., Des Marais, D. J., Sarrazin, P., Agard, C., Alves Verdasca, J. A., Anderson, R., Archer, D., Armiens-Aparicio, C., Arvidson, R., Atlaskin, E., Atreya, S., Aubrey, A., Baker, B., Baker, M., Balic-Zunic, T., Baratoux, D., Baroukh, J., Barraclough, B., Bean, K., Beegle, L., Behar, A., Bell, J., Bender, S., Benna, M., Bentz, J., Berger, G., Berger, J., Berman, D., Blanco Avalos, J. J., Blaney, D., Blank, J., Blau, H., Bleacher, L., Boehm, E., Botta, O., Bottcher, S., Boucher, T., Bower, H., Boyd, N., Boynton, B., Breves, E., Bridges, J., Brinckerhoff, W., Brinza, D., Brunet, C., Brunner, A., Brunner, W., Buch, A., Bullock, M., Burmeister, S., Cabane, M., Calef, F., Cameron, J., Cantor, B., Caplinger, M., Rodriguez, J. C., Carmosino, M., Blazquez, I. C., Charpentier, A., Choi, D., Clark, B., Clegg, S., Cleghorn, T., Cloutis, E., Cody, G., Coll, P., Conrad, P., Coscia, D., Cousin, A., Cremers, D., Cros, A., Cucinotta, F., d'Uston, C., Davis, S., Day, M., Juarez, M. d. l. T., DeFlores, L., DeLapp, D., DeMarines, J., Dietrich, W., Dingler, R., Donny, C., Drake, D., Dromart, G., Dupont, A., Duston, B., Dworkin, J., Dyar, M. D., Edgar, L., Edwards, C., Edwards, L., Ehlmann, B., Ehresmann, B., Eigenbrode, J., Elliott, B., Elliott, H., Ewing, R., Fabre, C., Fairen, A., Farley, K., Fassett, C., Favot, L., Fay, D., Fedosov, F., Feldman, J., Feldman, S., Fitzgibbon, M., Flesch, G., Floyd, M., Fluckiger, L., Fraeman, A., Francis, R., Francois, P., Franz, H., French, K. L., Frydenvang, J., Gaboriaud, A., Gailhanou, M., Garvin, J., Geffroy, C., Genzer, M., Godber, A., Goesmann, F., Golovin, D., Gomez, F. G., Gomez-Elvira, J., Gondet, B., Gordon, S., Gorevan, S., Grant, J., Griffes, J., Grinspoon, D., Guillemot, P., Guo, J., Gupta, S., Guzewich, S., Haberle, R., Halleaux, D., Hallet, B., Hamilton, V., Hardgrove, C., Harker, D., Harpold, D., Harri, A.-M., Harshman, K., Hassler, D., Haukka, H., Hayes, A., Herkenhoff, K., Herrera, P., Hettrich, S., Heydari, E., Hipkin, V., Hoehler, T., Hollingsworth, J., Hudgins, J., Huntress, W., Hurowitz, J., Hviid, S., Iagnemma, K., Indyk, S., Israel, G., Jackson, R., Jacob, S., Jakosky, B., Jensen, E., Jensen, J. K., Johnson, J., Johnson, M., Johnstone, S., Jones, A., Jones, J., Joseph, J., Jun, I., Kahanpaa, H., Kahre, M., Karpushkina, N., Kasprzak, W., Kauhanen, J., Keely, L., Kemppinen, O., Keymeulen, D., Kim, M.-H., Kinch, K., King, P., Kirkland, L., Koefoed, A., Kohler, J., Kortmann, O., Kozyrev, A., Krezoski, J., Krysak, D., Kuzmin, R., Lacour, J. L., Lafaille, V., Langevin, Y., Lanza, N., Lasue, J., Le Mouelic, S., Lee, E. M., Lee, Q.-M., Lees, D., Lefavor, M., Lemmon, M., Lepinette Malvitte, A., Leveille, R., Lewin-Carpintier, E., Li, S., Lipkaman, L., Little, C., Litvak, M., Lorigny, E., Lugmair, G., Lundberg, A., Lyness, E., Maki, J., Malakhov, A., Malespin, C., Malin, M., Mangold, N., Manning, H., Marchand, G., Marin Jimenez, M., Martin Garcia, C., Martin, D., Martin, M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Mauchien, P., McAdam, A., McCartney, E., McConnochie, T., McCullough, E., McEwan, I., McKay, C., McNair, S., Melikechi, N., Meyer, M., Mezzacappa, A., Miller, H., Miller, K., Milliken, R., Minitti, M., Mischna, M., Mitrofanov, I., Moersch, J., Mokrousov, M., Molina Jurado, A., Moores, J., Mora-Sotomayor, L., Morookian, J. M., Mueller-Mellin, R., Muller, J.-P., Munoz Caro, G., Nachon, M., Navarro Lopez, S., Nealson, K., Nefian, A., Nelson, T., Newcombe, M., Newman, C., Newsom, H., Nikiforov, S., Niles, P., Nixon, B., Dobrea, E. N., Nolan, T., Oehler, D., Ollila, A., Olson, T., Owen, T., Pablo, H., Paillet, A., Pallier, E., Palucis, M., Parker, T., Parot, Y., Patel, K., Paton, M., Paulsen, G., Pavlov, A., Pavri, B., Peinado-Gonzalez, V., Pepin, R., Peret, L., Perez, R., Perrett, G., Peterson, J., Pilorget, C., Pinet, P., Pla-Garcia, J., Plante, I., Poitrasson, F., Polkko, J., Popa, R., Posiolova, L., Pradler, I., Prats, B., Prokhorov, V., Purdy, S. W., Raaen, E., Radziemski, L., Rafkin, S., Ramos, M., Raulin, F., Ravine, M., Reitz, G., Renno, N., Rice, M., Richardson, M., Robert, F., Rodriguez Manfredi, J. A., Romeral-Planello, J. J., Rowland, S., Saccoccio, M., Salamon, A., Sandoval, J., Sanin, A., Sans Fuentes, S. A., Saper, L., Sautter, V., Savijarvi, H., Schieber, J., Schmidt, W., Scholes, D., Schoppers, M., Schroder, S., Sebastian Martinez, E., Sengstacken, A., Shterts, R., Siebach, K., Siili, T., Simmonds, J., Sirven, J.-B., Slavney, S., Sletten, R., Smith, M., Sobron Sanchez, P., Spanovich, N., Spray, J., Squyres, S., Stack, K., Stalport, F., Stein, T., Stern, J., Stewart, N., Stipp, S. L. S., Stoiber, K., Sucharski, B., Summons, R., Sun, V., Supulver, K., Sutter, B., Szopa, C., Tate, C., Teinturier, S., ten Kate, I. L., Thomas, P., Thompson, L., Tokar, R., Toplis, M., Torres Redondo, J., Trainer, M., Tretyakov, V., Urqui-O'Callaghan, R., Van Beek, J., Van Beek, T., VanBommel, S., Varenikov, A., Vasavada, A., Vasconcelos, P., Vicenzi, E., Vostrukhin, A., Voytek, M., Wadhwa, M., Ward, J., Webster, C., Weigle, E., Wellington, D., Westall, F., Wiens, R. C., Wilhelm, M. B., Williams, A., Williams, J., Williams, R., Williams, R. B., Wilson, M., Wimmer-Schweingruber, R., Wolff, M., Wong, M., Wray, J., Wu, M., Yana, C., Zeitlin, C., Zimdar, R., Zorzano Mier, M.-P., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), NASA Ames Research Center (ARC), NASA Johnson Space Center (JSC), NASA, Department of Geological Sciences [Austin], Jackson School of Geosciences (JSG), University of Texas at Austin [Austin]-University of Texas at Austin [Austin], Department of Geology [Tucson], University of Arizona, Department of Geological Sciences [Bloomington], Indiana University [Bloomington], Indiana University System-Indiana University System, Malin Space Science Systems (MSSS), NASA Goddard Space Flight Center (GSFC), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
Basalt, Meridiani Planum, Multidisciplinary, 010504 meteorology & atmospheric sciences, Curiosity rover, Geochemistry, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars Exploration Program, Exploration of Mars, 01 natural sciences, Astrobiology, Impact crater, 13. Climate action, MSL Mars Gale Crater Rocknest, Rocknest, 0103 physical sciences, Sample Analysis at Mars, Aeolian processes, MSL, Rocknest aeolian deposit, 010303 astronomy & astrophysics, Geology, 0105 earth and related environmental sciences
Abstract

The Rocknest aeolian deposit is similar to aeolian features analyzed by the Mars Exploration Rovers (MERs) Spirit and Opportunity. The fraction of sand

Published
2013
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16. The Petrochemistry of Jake_M: A Martian Mugearite

Author

Stolper, E. M., Baker, M. B., Newcombe, M. E., Schmidt, M. E., Treiman, A. H., Cousin, A., Dyar, M. D., Fisk, M. R., Gellert, R., King, P. L., Leshin, L., Maurice, S., McLennan, S. M., Minitti, M. E., Perrett, G., Rowland, S., Sautter, V., Wiens, R. C., Kemppinen, O., Bridges, N., Johnson, J. R., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., Blank, J., Weigle, G., Li, S., Milliken, R., Robertson, K., Sun, V., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Grotzinger, J., Miller, H., Pilorget, C., Rice, M., Siebach, K., Stack, K., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Squyres, S., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Teinturier, S., Dromart, G., Robert, F., Le Mouelic, S., Mangold, N., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Cameron, J., Clegg, S., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Williams, R. B., Kirkland, L., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Conrad, P., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Harpold, D., Mahaffy, P., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Trainer, M., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A., Webster, C. R., Yen, A., Archer, P. D., Cucinotta, F., Jones, J. H., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Jones, A., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Navarro-Gonzalez, R., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Sumner, D. Y., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Pradler, I., VanBommel, S., Jacob, S., Owen, T., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Franz, H., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Atreya, S., Elliott, H., Halleaux, D., Renno, N., Wong, M., Pepin, R., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., GeoRessources, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS), California Institute of Technology (CALTECH), Department of Earth Sciences [St. Catharines], Brock University [Canada], Lunar and Planetary Institute [Houston] (LPI), Los Alamos National Laboratory (LANL), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Mount Holyoke College, Oregon State University (OSU), University of Guelph, Research School of Earth Sciences [Canberra] (RSES), Australian National University (ANU), Rensselaer Polytechnic Institute (RPI), State University of New York (SUNY), Johns Hopkins University Applied Physics Laboratory [Laurel, MD] (APL), University of Hawaii, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), MSL Science Team, Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), and Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010504 meteorology & atmospheric sciences, Curiosity rover, Geochemistry, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, 010502 geochemistry & geophysics, 01 natural sciences, Jake_M: a martian mugearite, chemistry.chemical_compound, Nepheline, MSL, Chemical composition, 0105 earth and related environmental sciences, Martian, Phonolite, Multidisciplinary, Fractional crystallization (geology), petrochemistry, Igneous rock, Planetary science, MSL Mars Petrochemistry, chemistry, 13. Climate action, Petrochemistry, Geology, [SDU.STU.MI]Sciences of the Universe [physics]/Earth Sciences/Mineralogy
Abstract

International audience; "Jake_M," the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the Curiosity rover, differs substantially in chemical composition from other known martian igneous rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been produced by extensive fractional crystallization of a primary alkaline or transitional magma at elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter even more fractionated alkaline rocks (for example, phonolites and trachytes).

Published
2013
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17. Volatile, Isotope, and Organic Analysis of Martian Fines with the Mars Curiosity Rover

Author

Leshin, L. A., Mahaffy, P. R., Webster, C. R., Cabane, M., Coll, P., Conrad, P. G., Archer, P. D., Atreya, S. K., Brunner, A. E., Buch, A., Eigenbrode, J. L., Flesch, G. J., Franz, H. B., Freissinet, C., Glavin, D. P., McAdam, A. C., Miller, K. E., Ming, D. W., Morris, R. V., Navarro-Gonzalez, R., Niles, P. B., Owen, T., Pepin, R. O., Squyres, S., Steele, A., Stern, J. C., Summons, R. E., Sumner, D. Y., Sutter, B., Szopa, C., Teinturier, S., Trainer, M. G., Wray, J. J., Grotzinger, J. P., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stack, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Maurice, S., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Coscia, D., Dromart, G., Robert, F., Sautter, V., Le Mouelic, S., Mangold, N., Nachon, M., Stalport, F., Francois, P., Raulin, F., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Wiens, R. C., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Dworkin, J. P., Floyd, M., Garvin, J., Harpold, D., Martin, D. K., Pavlov, A., Raaen, E., Smith, M. D., Tan, F., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A. R., Yen, A., Cucinotta, F., Jones, J. H., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Bower, H., Blau, H., Boucher, T., Carmosino, M., Elliott, H., Halleaux, D., Renno, N., Wong, M., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., Department of Earth and Environmental Sciences [Troy, NY], Rensselaer Polytechnic Institute (RPI), NASA Goddard Space Flight Center (GSFC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), PLANETO - LATMOS, Laboratoire Atmosphères, Milieux, Observations Spatiales (LATMOS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Astromaterials Research and Exploration Science (ARES), NASA Johnson Space Center (JSC), NASA-NASA, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Astronomy [College Park], University of Maryland [College Park], University of Maryland System-University of Maryland System, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Center for Research and Exploration in Space Science and Technology [GSFC] (CRESST), Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Massachusetts Institute of Technology (MIT), Laboratorio de Química de Plasmas y Estudios Planetarios [Mexico], Instituto de Ciencias Nucleares [Mexico], Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institute for Astronomy [Honolulu], University of Hawai‘i [Mānoa] (UHM), School of Physics and Astronomy [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Cornell University [New York], Geophysical Laboratory [Carnegie Institution], Carnegie Institution for Science, University of California [Davis] (UC Davis), University of California (UC), Jacobs Technology ESCG, Institut Pierre-Simon-Laplace (IPSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), School of Earth and Atmospheric Sciences [Atlanta], Georgia Institute of Technology [Atlanta], Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, Petrology, California Institute of Technology (CALTECH)-NASA, Universidad Nacional Autónoma de México (UNAM)-Universidad Nacional Autónoma de México (UNAM), Carnegie Institution for Science [Washington], University of California, École normale supérieure - Paris (ENS Paris), IMPEC - LATMOS, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Minnesota [Twin Cities], Cornell University, and École normale supérieure - Paris (ENS Paris)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National d'Études Spatiales [Toulouse] (CNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)

Subjects
Martian, Multidisciplinary, 010504 meteorology & atmospheric sciences, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Thermal decomposition, Curiosity rover, [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], chemistry.chemical_element, Mars, organic analysis, Mars Exploration Program, 01 natural sciences, Astrobiology, chemistry.chemical_compound, chemistry, 13. Climate action, Isotopes of carbon, Rocknest, 0103 physical sciences, Sample Analysis at Mars, Carbonate, MSL Mars Volatiles Isotopes Organics Soil Gale Crater, 010303 astronomy & astrophysics, Carbon, 0105 earth and related environmental sciences
Abstract

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity’s Sample Analysis at Mars instrument suite. H 2 O, SO 2 , CO 2 , and O 2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H 2 O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO 2 . Evolved O 2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

Published
2013
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18. X-ray diffraction results from mars science laboratory: Mineralogy of rocknest at Gale crater

Author

Bish, D. L., Blake, D. F., Vaniman, D. T., Chipera, S. J., Morris, R. V., Ming, D. W., Treiman, A. H., Sarrazin, P., Morrison, S. M., Downs, R. T., Achilles, C. N., Yen, A. S., Bristow, T. F., Crisp, J. A., Morookian, J. M., Farmer, J. D., Rampe, E. B., Stolper, E. M., Spanovich, N., Achilles, C., Agard, C., Verdasca, J. A. A., Anderson, R., Archer, D., Armiens-Aparicio, C., Arvidson, R., Atlaskin, E., Atreya, S., Aubrey, A., Baker, B., Baker, M., Balic-Zunic, T., Baratoux, D., Baroukh, J., Barraclough, B., Bean, K., Beegle, L., Behar, A., Bell, J., Bender, S., Benna, M., Bentz, J., Berger, G., Berger, J., Berman, D., Bish, D., Avalos, J. J. B., Blaney, D., Blank, J., Blau, H., Bleacher, L., Boehm, E., Botta, O., Bottcher, S., Boucher, T., Bower, H., Boyd, N., Boynton, B., Breves, E., Bridges, J., Bridges, N., Brinckerhoff, W., Brinza, D., Bristow, T., Brunet, C., Brunner, A., Brunner, W., Buch, A., Bullock, M., Burmeister, S., Cabane, M., Calef, F., Cameron, J., Campbell, J. I., Cantor, B., Caplinger, M., Rodriguez, J. C., Carmosino, M., Blazquez, I. C., Charpentier, A., Chipera, S., Choi, D., Clark, B., Clegg, S., Cleghorn, T., Cloutis, E., Cody, G., Coll, P., Conrad, P., Coscia, D., Cousin, A., Cremers, D., Crisp, J., Cros, A., Cucinotta, F., d'Uston, C., Davis, S., Day, M. K., Juarez, M. d. l. T., DeFlores, L., DeLapp, D., DeMarines, J., DesMarais, D., Dietrich, W., Dingler, R., Donny, C., Downs, B., Drake, D., Dromart, G., Dupont, A., Duston, B., Dworkin, J., Dyar, M. D., Edgar, L., Edgett, K., Edwards, C., Edwards, L., Ehlmann, B., Ehresmann, B., Eigenbrode, J., Elliott, B., Elliott, H., Ewing, R., Fabre, C., Fairen, A., Farley, K., Farmer, J., Fassett, C., Favot, L., Fay, D., Fedosov, F., Feldman, J., Feldman, S., Fisk, M., Fitzgibbon, M., Flesch, G., Floyd, M., Fluckiger, L., Forni, O., Fraeman, A., Francis, R., Francois, P., Franz, H., Freissinet, C., French, K. L., Frydenvang, J., Gaboriaud, A., Gailhanou, M., Garvin, J., Gasnault, O., Geffroy, C., Gellert, R., Genzer, M., Glavin, D., Godber, A., Goesmann, F., Goetz, W., Golovin, D., Gomez, F. G., Gomez-Elvira, J., Gondet, B., Gordon, S., Gorevan, S., Grant, J., Griffes, J., Grinspoon, D., Grotzinger, J., Guillemot, P., Guo, J., Gupta, S., Guzewich, S., Haberle, R., Halleaux, D., Hallet, B., Hamilton, V., Hardgrove, C., Harker, D., Harpold, D., Harri, A.-M., Harshman, K., Hassler, D., Haukka, H., Hayes, A., Herkenhoff, K., Herrera, P., Hettrich, S., Heydari, E., Hipkin, V., Hoehler, T., Hollingsworth, J., Hudgins, J., Huntress, W., Hurowitz, J., Hviid, S., Iagnemma, K., Indyk, S., Israel, G., Jackson, R., Jacob, S., Jakosky, B., Jensen, E., Jensen, J. K., Johnson, J., Johnson, M., Johnstone, S., Jones, A., Jones, J., Joseph, J., Jun, I., Kah, L., Kahanpaa, H., Kahre, M., Karpushkina, N., Kasprzak, W., Kauhanen, J., Keely, L., Kemppinen, O., Keymeulen, D., Kim, M.-H., Kinch, K., King, P., Kirkland, L., Kocurek, G., Koefoed, A., Kohler, J., Kortmann, O., Kozyrev, A., Krezoski, J., Krysak, D., Kuzmin, R., Lacour, J. L., Lafaille, V., Langevin, Y., Lanza, N., Lasue, J., Le Mouelic, S., Lee, E. M., Lee, Q.-M., Lees, D., Lefavor, M., Lemmon, M., Malvitte, A. L., Leshin, L., Leveille, R., Lewin-Carpintier, E., Lewis, K., Li, S., Lipkaman, L., Little, C., Litvak, M., Lorigny, E., Lugmair, G., Lundberg, A., Lyness, E., Madsen, M., Mahaffy, P., Maki, J., Malakhov, A., Malespin, C., Malin, M., Mangold, N., Manhes, G., Manning, H., Marchand, G., Jimenez, M. M., Garcia, C. M., Martin, D., Martin, M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Mauchien, P., Maurice, S., McAdam, A., McCartney, E., McConnochie, T., McCullough, E., McEwan, I., McKay, C., McLennan, S., McNair, S., Melikechi, N., Meslin, P.-Y., Meyer, M., Mezzacappa, A., Miller, H., Miller, K., Milliken, R., Ming, D., Minitti, M., Mischna, M., Mitrofanov, I., Moersch, J., Mokrousov, M., Jurado, A. M., Moores, J., Mora-Sotomayor, L., Morris, R., Morrison, S., Mueller-Mellin, R., Muller, J.-P., Caro, G. M., Nachon, M., Lopez, S. N., Navarro-Gonzalez, R., Nealson, K., Nefian, A., Nelson, T., Newcombe, M., Newman, C., Newsom, H., Nikiforov, S., Niles, P., Nixon, B., Dobrea, E. N., Nolan, T., Oehler, D., Ollila, A., Olson, T., Owen, T., Hernandez, M. A. d. P., Paillet, A., Pallier, E., Palucis, M., Parker, T., Parot, Y., Patel, K., Paton, M., Paulsen, G., Pavlov, A., Pavri, B., Peinado-Gonzalez, V., Pepin, R., Peret, L., Perez, R., Perrett, G., Peterson, J., Pilorget, C., Pinet, P., Pla-Garcia, J., Plante, I., Poitrasson, F., Polkko, J., Popa, R., Posiolova, L., Posner, A., Pradler, I., Prats, B., Prokhorov, V., Purdy, S. W., Raaen, E., Radziemski, L., Rafkin, S., Ramos, M., Rampe, E., Raulin, F., Ravine, M., Reitz, G., Renno, N., Rice, M., Richardson, M., Robert, F., Robertson, K., Manfredi, J. A. R., Romeral-Planello, J. J., Rowland, S., Rubin, D., Saccoccio, M., Salamon, A., Sandoval, J., Sanin, A., Fuentes, S. A. S., Saper, L., Sautter, V., Savijarvi, H., Schieber, J., Schmidt, M., Schmidt, W., Scholes, D. D., Schoppers, M., Schroder, S., Schwenzer, S., Martinez, E. S., Sengstacken, A., Shterts, R., Siebach, K., Siili, T., Simmonds, J., Sirven, J.-B., Slavney, S., Sletten, R., Smith, M., Sanchez, P. S., Spray, J., Squyres, S., Stack, K., Stalport, F., Steele, A., Stein, T., Stern, J., Stewart, N., Stipp, S. L. S., Stoiber, K., Stolper, E., Sucharski, B., Sullivan, R., Summons, R., Sumner, D., Sun, V., Supulver, K., Sutter, B., Szopa, C., Tan, F., Tate, C., Teinturier, S., ten Kate, I., Thomas, P., Thompson, L., Tokar, R., Toplis, M., Redondo, J. T., Trainer, M., Treiman, A., Tretyakov, V., Urqui-O'Callaghan, R., Van Beek, J., Van Beek, T., VanBommel, S., Vaniman, D., Varenikov, A., Vasavada, A., Vasconcelos, P., Vicenzi, E., Vostrukhin, A., Voytek, M., Wadhwa, M., Ward, J., Webster, C., Weigle, E., Wellington, D., Westall, F., Wiens, R. C., Wilhelm, M. B., Williams, A., Williams, J., Williams, R., Williams, R. B. M., Wilson, M., Wimmer-Schweingruber, R., Wolff, M., Wong, M., Wray, J., Wu, M., Yana, C., Yen, A., Yingst, A., Zeitlin, C., Zimdar, R., Mier, M.-P. Z., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
Multidisciplinary, 010504 meteorology & atmospheric sciences, Water on Mars, Curiosity rover, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mineralogy, Mars, Mars Exploration Program, Martian soil, engineering.material, 01 natural sciences, MSL Mars X-ray Diffraction Mineralogy Rocknest Gale Crater, Meteorite, Impact crater, 13. Climate action, Rocknest, 0103 physical sciences, Pigeonite, engineering, Composition of Mars, MSL, 010303 astronomy & astrophysics, 0105 earth and related environmental sciences, mineralogy of Rocknest at Gale crater
Abstract

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe 3+ - and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii.

Published
2013
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19. Ser-256 phosphorylation dynamics of Aquaporin 2 during maturation from the ER to the vesicular compartment in renal cells

Author

Procino, G., Carmosino, M., Marin, Oriano, Brunati, ANNA MARIA, Contri, Antonella, Pinna, Lorenzo, Mannucci, R., Nielsen, S., Kwon, T. H., Svelto, M., and Valenti, G.

Subjects
Aquaporin 2, Synthetic peptides, Golgi Apparatus, Diabetes Insipidus, Nephrogenic, Protein Serine-Threonine Kinases, Aquaporins, Endoplasmic Reticulum, Kidney, Models, Biological, Aquaporin 6, Cell Line, Protein Transport, Protein phosphorylation, Consensus Sequence, Mutation, Serine, Humans, Phosphorylation, Lysosomes, Transport Vesicles
Abstract

Aquaporin 2 (AQP2) phosphorylation at Ser-256 by protein kinase A (PKA) is a key signal for vasopressin-stimulated AQP2 insertion into the plasma membrane in renal cells. This study underscores the possible role of phosphorylation at Ser-256 in regulating AQP2 maturation. AQP2-transfected renal CD8 cells were incubated with brefeldin A (BFA) to accumulate newly synthesized AQP2 in the endoplasmic reticulum (ER), and AQP2 flow from ER to the vesicular compartment was analyzed after BFA washout. We found that a) in the ER, AQP2 is weakly phosphorylated; b) the amount of phosphorylated AQP2 (p-AQP2) at Ser-256 increased significantly during transit in the Golgi, even in the presence of the PKA inhibitor H89; and c) AQP2 transport from the Golgi to the vasopressin-regulated vesicular compartment occurred with a concomitant decrease in p-AQP2 at Ser-256. These results support the hypothesis that AQP2 transition in the Golgi apparatus is associated with a PKA-independent increase in AQP2 phosphorylation at Ser-256. Conversely, impaired constitutive phosphorylation in a Golgi-associated compartment occurring in cells expressing mutated S256A-AQP2 or E258K-AQP2 causes phosphorylation-defective AQP2 routing to lysosomes. This result might explain the molecular basis of the dominant form of nephrogenic diabetes insipidus caused by the mutation E258K-AQP2, in which the phenotype is caused by an impaired routing of AQP2.

Published
2003

21. Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human gastric cells.

Author

Carmosino, M., Procino, G., Tamma, G., Mannucci, R., Svelto, M., Valenti, G., Carmosino, M., Procino, G., Tamma, G., Mannucci, R., Svelto, M., and Valenti, G.

Abstract

Item does not contain fulltext, BACKGROUND INFORMATION: AQP4 (aquaporin 4) internalization and a concomitant decrease in the osmotic water permeability coefficient (Pf) after histamine exposure has been reported in AQP4-transfected gastric HGT1 cells. RESULTS: In the present study we report that AQP4 internalization is followed by an increase in AQP4 phosphorylation. Histamine treatment for 30 min resulted in an approx. 10-fold increase in AQP4 phosphorylation that was inhibited by 1 microM H89, a specific PKA (protein kinase A) inhibitor, but not by PKC (protein kinase C) and CK2 inhibitors. Moreover, measurement of PKA activity after 30 min of histamine treatment showed that PKA activity was approx. 3-fold higher compared with basal conditions. AQP4 phosphorylation was prevented in cells treated with histamine for 30 min after pre-incubation with PAO (phenylarsine oxide), an inhibitor of protein endocytosis. Using an endo-exocytosis assay we showed that, after histamine washed out, internalized AQP4 recycled back to the cell surface, even in cells in which de novo protein synthesis was inhibited by cycloheximide. CONCLUSIONS: Phosphorylation experiments, combined with immunolocalization studies, indicated that AQP4 phosphorylation is mediated by PKA and occurs subsequently to its internalization in late endosomes. We suggest that phosphorylation might be a mechanism involved in retaining AQP4 in a vesicle-recycling compartment.

Published
2007

22. Accurate determination of ferric iron in garnets by bulk Mossbauer spectroscopy and synchrotron micro-XANES

Author

Dyar, M. D., primary, Breves, E. A., additional, Emerson, E., additional, Bell, S. W., additional, Nelms, M., additional, Ozanne, M. V., additional, Peel, S. E., additional, Carmosino, M. L., additional, Tucker, J. M., additional, Gunter, M. E., additional, Delaney, J. S., additional, Lanzirotti, A., additional, and Woodland, A. B., additional

Published
2012
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26. The differential diagnosis of Axis I psychopathology presenting to a university-based multiple sclerosis clinic.

Author

Brousseau, K. M., Arciniegas, D. B., Carmosino, M. J., and Corboy, J. R.

Subjects
MULTIPLE sclerosis, PATHOLOGICAL psychology, PSYCHIATRIC diagnosis, SOMATOFORM disorders, ANXIETY disorders, NEUROBEHAVIORAL disorders
Abstract

Patients carrying a presumptive diagnosis of multiple sclerosis (MS) sometimes present with nonspecific clinical signs and symptoms that may be, at least in part, somatic manifestations of psychiatric conditions. This retrospective study was undertaken to identify psychiatric diagnoses among 63 patients whose initial clinical evaluations suggested a primary psychiatric, rather than a primary neurological, etiology for their symptoms. Some 92% of patients met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) criteria for one or more primary psychiatric disorders, most often including somatoform, mood, and anxiety disorders. Accurate identification and diagnosis of psychiatric conditions producing pseudoneurological or non-specific somatic symptoms is necessary for both treatment and medico-economic reasons. [ABSTRACT FROM AUTHOR]

Published
2007
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27. Molecular basis of antihypertensive effect of bradikinin: functional involvement of renal aquaporins.

Author

VALENTI, G., TAMMA, G., CARMOSINO, M., and SVELTO, M.

Abstract

Bradykinin (BK) is one of the most important peptide regulating vascular tone, water, and ionic balance in the body, playing a key role in controlling blood pressure. Interestingly, patients with essential hypertension excrete less BK than do normotensive subjects. To elucidate the mechanism by which BK regulates renal water transport, AQP2-transfected collecting duct CD8 cells, expressing the BK receptor (BK2), were used as experimental model. In CD8 cells, BK pretreatment impaired forskolin-induced AQP2 translocation to the apical plasma membrane. To clarify the signal transduction cascade associated with this effect, we first investigated whether BK induced increase in citosolic calcium, via the G protein Gq known to be coupled to BK2 receptor. Spectrofluorometry employing fura-2-AM revealed that 100 nM BK elicited a significant increase in Cai (from 72.8 ± 7.4, to 310.7 ± 43.4 nM, n=6, P which was abolished by the receptor antagonist HOE-140. In renal cells, Gq coupled receptors may activate Rho and its downstream effectors. In CD8 cells it has been shown that forskolin-induced AQP2 translocation is associated with a decrease in Rho activity and depolymerization of F-actin which facilitates the translocation of AQP2 to the plasma membrane. Interestingly, BK treatment in CD8 cells resulted in a significant increase in Rho activity, as assessed by selective pull down experiments. In agreement with these data, BK induced a significant increase of F-actin content as assessed by actin polymerization assay and by immunofluorescence experiments. BK effects on actin assembly were abolished by the BK2 agonist HOE-140. We conclude that the diuretic effect of bradykinin may in part be explained by impairement of AQP2 translocation via activation of Rho and F-actin formation. [ABSTRACT FROM AUTHOR]

Published
2019

28. The multifunctional polydnavirus TnBVANK1 protein: impact on host apoptotic pathway

Author

Chiara Giangrande, Marisa Nardiello, Heiko Vogel, Gerarda Grossi, Vitalba Ruggieri, Rosanna Salvia, Patrizia Falabella, Sabino Aurelio Bufo, Monica Carmosino, S. Bradleigh Vinson, David Neunemann, Pietro Pucci, Angela Amoresano, Carmen Scieuzo, Ilaria Laurenzana, Salvia, R, Grossi, G, Amoresano, Angela, Scieuzo, C, Nardiello, M, Giangrande, C, Laurenzana, I, Ruggieri, V, Bufo, Sa, Vinson, Sb, Carmosino, M, Neunemann, D, Vogel, H, Pucci, Pietro, and Falabella, P.

Subjects
0301 basic medicine, Hemocytes, food.ingredient, Immunoprecipitation, lcsh:Medicine, Apoptosis, Article, Viral Proteins, 03 medical and health sciences, food, Transcription (biology), RNA interference, Botany, Animals, lcsh:Science, Gene, Multidisciplinary, 030102 biochemistry & molecular biology, biology, Heliothis virescens, Schneider 2 cells, Polydnavirus, lcsh:R, fungi, biology.organism_classification, Cell biology, Lepidoptera, 030104 developmental biology, Polydnaviridae, lcsh:Q, Bracovirus
Abstract

Toxoneuron nigriceps (Hymenoptera, Braconidae) is an endophagous parasitoid of the larval stages of the tobacco budworm, Heliothis virescens (Lepidoptera, Noctuidae). The bracovirus associated with this wasp (TnBV) is currently being studied. Several genes expressed in parasitised host larvae have been isolated and their possible roles partly elucidated. TnBVank1 encodes an ankyrin motif protein similar to insect and mammalian IκB, an inhibitor of the transcription nuclear factor κB (NF-κB). Here we show that, when TnBVank1 was stably expressed in polyclonal Drosophila S2 cells, apoptosis is induced. Furthermore, we observed the same effects in haemocytes of H. virescens larvae, after TnBVank1 in vivo transient transfection, and in haemocytes of parasitised larvae. Coimmunoprecipitation experiments showed that TnBVANK1 binds to ALG-2 interacting protein X (Alix/AIP1), an interactor of apoptosis-linked gene protein 2 (ALG-2). Using double-immunofluorescence labeling, we observed the potential colocalization of TnBVANK1 and Alix proteins in the cytoplasm of polyclonal S2 cells. When Alix was silenced by RNA interference, TnBVANK1 was no longer able to cause apoptosis in both S2 cells and H. virescens haemocytes. Collectively, these results indicate that TnBVANK1 induces apoptosis by interacting with Alix, suggesting a role of TnBVANK1 in the suppression of host immune response observed after parasitisation by T. nigriceps.

Published
2017
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30. The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

Author

Milano S, Saponara I, Gerbino A, Carmosino M, Svelto M, and Procino G

Subjects
Male, Animals, Mice, Inbred C57BL, Disease Models, Animal, Antidiuretic Agents pharmacology, Antidiuretic Agents therapeutic use, Kidney Concentrating Ability drug effects, Polydipsia drug therapy, Polydipsia etiology, Adrenergic beta-3 Receptor Agonists pharmacology, Adrenergic beta-3 Receptor Agonists therapeutic use
Abstract

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the β3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human β3-AR agonists might represent an effective possible treatment strategy for X-NDI., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Published
2024
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31. β3-Adrenoceptor as a new player in the sympathetic regulation of the renal acid-base homeostasis.

Author

Milano S, Saponara I, Gerbino A, Lapi D, Lela L, Carmosino M, Dal Monte M, Bagnoli P, Svelto M, and Procino G

Abstract

Efferent sympathetic nerve fibers regulate several renal functions activating norepinephrine receptors on tubular epithelial cells. Of the beta-adrenoceptors (β-ARs), we previously demonstrated the renal expression of β3-AR in the thick ascending limb (TAL), the distal convoluted tubule (DCT), and the collecting duct (CD), where it participates in salt and water reabsorption. Here, for the first time, we reported β3-AR expression in the CD intercalated cells (ICCs), where it regulates acid-base homeostasis. Co-localization of β3-AR with either proton pump H + -ATPase or Cl - /HCO 3 - exchanger pendrin revealed β3-AR expression in type A, type B, non-A, and non-B ICCs in the mouse kidney. We aimed to unveil the possible regulatory role of β3-AR in renal acid-base homeostasis, in particular in modulating the expression, subcellular localization, and activity of the renal H + -ATPase, a key player in this process. The abundance of H + -ATPase was significantly decreased in the kidneys of β3-AR -/- compared with those of β3-AR +/+ mice. In particular, H + -ATPase reduction was observed not only in the CD but also in the TAL and DCT, which contribute to acid-base transport in the kidney. Interestingly, we found that in in vivo , the absence of β3-AR reduced the kidneys' ability to excrete excess proton in the urine during an acid challenge. Using ex vivo stimulation of mouse kidney slices, we proved that the β3-AR activation promoted H + -ATPase apical expression in the epithelial cells of β3-AR-expressing nephron segments, and this was prevented by β3-AR antagonism or PKA inhibition. Moreover, we assessed the effect of β3-AR stimulation on H + -ATPase activity by measuring the intracellular pH recovery after an acid load in β3-AR-expressing mouse renal cells. Importantly, β3-AR agonism induced a 2.5-fold increase in H + -ATPase activity, and this effect was effectively prevented by β3-AR antagonism or by inhibiting either H + -ATPase or PKA. Of note, in urine samples from patients treated with a β3-AR agonist, we found that β3-AR stimulation increased the urinary excretion of H + -ATPase, likely indicating its apical accumulation in tubular cells. These findings demonstrate that β3-AR activity positively regulates the expression, plasma membrane localization, and activity of H + -ATPase, elucidating a novel physiological role of β3-AR in the sympathetic control of renal acid-base homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Milano, Saponara, Gerbino, Lapi, Lela, Carmosino, Dal Monte, Bagnoli, Svelto and Procino.)

Published
2024
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32. Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y.

Author

Nigro I, Miglionico R, Carmosino M, Gerbino A, Masato A, Sandre M, Bubacco L, Antonini A, Rinaldi R, Bisaccia F, and Armentano MF

Subjects
Humans, Cell Line, Hepatitis B virus, Clone Cells, Neuroprotective Agents pharmacology, Neuroblastoma, Hepatitis B, Neurodegenerative Diseases
Abstract

Up-regulated Gene clone 7 (URG7) is a protein localized in the endoplasmic reticulum (ER) and overexpressed in liver cells upon hepatitis B virus (HBV) infection. Its activity has been related to the attenuation of ER stress resulting from HBV infection, promoting protein folding and ubiquitination and reducing cell apoptosis overall. While the antiapoptotic activity of URG7 in HBV-infected cells may have negative implications, this effect could be exploited positively in the field of proteinopathies, such as neurodegenerative diseases. In this work, we aimed to verify the possible contribution of URG7 as a reliever of cellular proteostasis alterations in a neuronal in vitro system. Following tunicamycin-induced ER stress, URG7 was shown to modulate different markers of the unfolded protein response (UPR) in favor of cell survival, mitigating ER stress and activating autophagy. Furthermore, URG7 promoted ubiquitination, and determined a reduction in protein aggregation, calcium release from the ER and intracellular ROS content, confirming its pro-survival activity. Therefore, in light of the results reported in this work, we hypothesize that URG7 offers activity as an ER stress reliever in a neuronal in vitro model, and we paved the way for a new approach in the treatment of neurodegenerative diseases., Competing Interests: The authors declare no conflicts of interest.

Published
2023
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33. Targeting unfolded protein response reverts ER stress and ER Ca 2+ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/C R321X.

Author

Pietrafesa G, De Zio R, Scorza SI, Armentano MF, Pepe M, Forleo C, Procino G, Gerbino A, Svelto M, and Carmosino M

Subjects
Humans, Apoptosis, eIF-2 Kinase genetics, eIF-2 Kinase metabolism, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress, Guanabenz pharmacology, Homeostasis, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Unfolded Protein Response, Lamin Type A genetics, Lamin Type A metabolism, Myocytes, Cardiac metabolism
Abstract

Background: We previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DCM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/C protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-CHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac cells., Methods: HL-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2α, ATF4, CHOP and PARP-CL. In addition, we measured ER-dependent intracellular Ca 2+ dynamics as indicator of proper ER functionality., Results: We found that salubrinal and guanabenz increased the expression levels of phospho-eIF2α and downregulated the apoptosis markers CHOP and PARP-CL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle Ca 2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers CHOP and PARP-CL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular Ca 2+ was also restored in these cardiomyocytes., Conclusions: We provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes and to preserve the ER homeostasis in R321X LMNA-cardiomyocytes. Of note, two of the tested drugs, guanabenz and empagliflozin, are already used in the clinical practice, thus providing preclinical evidence for ready-to-use therapies in patients affected by the LMNA R321X associated cardiomyocytes., (© 2023. The Author(s).)

Published
2023
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34. TRPML1-Induced Lysosomal Ca 2+ Signals Activate AQP2 Translocation and Water Flux in Renal Collecting Duct Cells.

Author

Scorza SI, Milano S, Saponara I, Certini M, De Zio R, Mola MG, Procino G, Carmosino M, Moccia F, Svelto M, and Gerbino A

Subjects
Animals, Mice, Macrolides pharmacology, Macrolides metabolism, Aquaporin 2 genetics, Aquaporin 2 metabolism, Lysosomes genetics, Lysosomes metabolism, Water metabolism, Kidney Tubules, Collecting cytology, Kidney Tubules, Collecting metabolism
Abstract

Lysosomes are acidic Ca 2+ storage organelles that actively generate local Ca 2+ signaling events to regulate a plethora of cell functions. Here, we characterized lysosomal Ca 2+ signals in mouse renal collecting duct (CD) cells and we assessed their putative role in aquaporin 2 (AQP2)-dependent water reabsorption. Bafilomycin A1 and ML-SA1 triggered similar Ca 2+ oscillations, in the absence of extracellular Ca 2+ , by alkalizing the acidic lysosomal pH or activating the lysosomal cation channel mucolipin 1 (TRPML1), respectively. TRPML1-dependent Ca 2+ signals were blocked either pharmacologically or by lysosomes' osmotic permeabilization, thus indicating these organelles as primary sources of Ca 2+ release. Lysosome-induced Ca 2+ oscillations were sustained by endoplasmic reticulum (ER) Ca 2+ content, while bafilomycin A1 and ML-SA1 did not directly interfere with ER Ca 2+ homeostasis per se. TRPML1 activation strongly increased AQP2 apical expression and depolymerized the actin cytoskeleton, thereby boosting water flux in response to an hypoosmotic stimulus. These effects were strictly dependent on the activation of the Ca 2+ /calcineurin pathway. Conversely, bafilomycin A1 led to perinuclear accumulation of AQP2 vesicles without affecting water permeability. Overall, lysosomal Ca 2+ signaling events can be differently decoded to modulate Ca 2+ -dependent cellular functions related to the dock/fusion of AQP2-transporting vesicles in principal cells of the CD.

Published
2023
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35. β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus.

Author

Milano S, Maqoud F, Rutigliano M, Saponara I, Carmosino M, Gerbino A, Lucarelli G, Battaglia M, Svelto M, and Procino G

Subjects
Mice, Animals, Humans, Aquaporin 2 genetics, Aquaporin 2 metabolism, Polyuria drug therapy, Adrenergic beta-Agonists, Diabetes Insipidus, Nephrogenic drug therapy, Diabetes Insipidus, Nephrogenic genetics, Diabetes Insipidus, Nephrogenic metabolism, Diabetes Mellitus
Abstract

We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.

Published
2023
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36. Role of Nuclear Lamin A/C in the Regulation of Nav1.5 Channel and Microtubules: Lesson From the Pathogenic Lamin A/C Variant Q517X.

Author

De Zio R, Pietrafesa G, Milano S, Procino G, Bramerio M, Pepe M, Forleo C, Favale S, Svelto M, Gerbino A, and Carmosino M

Abstract

In this work, we studied an lmna nonsense mutation encoding for the C-terminally truncated Lamin A/C (LMNA) variant Q517X, which was described in patients affected by a severe arrhythmogenic cardiomyopathy with history of sudden death. We found that LMNA Q517X stably expressed in HL-1 cardiomyocytes abnormally aggregates at the nuclear envelope and within the nucleoplasm. Whole-cell patch clamp experiments showed that LMNA Q517X-expressing cardiomyocytes generated action potentials with reduced amplitude, overshoot, upstroke velocity and diastolic potential compared with LMNA WT-expressing cardiomyocytes. Moreover, the unique features of these cardiomyocytes were 1) hyper-polymerized tubulin network, 2) upregulated acetylated α-tubulin, and 3) cell surface Nav1.5 downregulation. These findings pointed the light on the role of tubulin and Nav1.5 channel in the abnormal electrical properties of LMNA Q517X-expressing cardiomyocytes. When expressed in HEK293 with Nav1.5 and its β1 subunit, LMNA Q517X reduced the peak Na + current (I Na ) up to 63% with a shift toward positive potentials in the activation curve of the channel. Of note, both AP properties in cardiomyocytes and Nav1.5 kinetics in HEK293 cells were rescued in LMNA Q517X-expressing cells upon treatment with colchicine, an FDA-approved inhibitor of tubulin assembly. In conclusion, LMNA Q517X expression is associated with hyper-polymerization and hyper-acetylation of tubulin network with concomitant downregulation of Nav1.5 cell expression and activity, thus revealing 1) new mechanisms by which LMNA may regulate channels at the cell surface in cardiomyocytes and 2) new pathomechanisms and therapeutic targets in cardiac laminopathies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Zio, Pietrafesa, Milano, Procino, Bramerio, Pepe, Forleo, Favale, Svelto, Gerbino and Carmosino.)

Published
2022
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37. Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies.

Author

Gerbino A, Forleo C, Milano S, Piccapane F, Procino G, Pepe M, Piccolo M, Guida P, Resta N, Favale S, Svelto M, and Carmosino M

Subjects
Adult, Cardiolipins metabolism, Cell Line, Female, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, HEK293 Cells, Humans, Male, Middle Aged, Recombinant Proteins metabolism, Cytokines metabolism, Heart Diseases metabolism, Inflammation metabolism
Abstract

Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30 serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients' sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1β IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70 kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Published
2021
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38. Aquaporin-1 Facilitates Transmesothelial Water Permeability: In Vitro and Ex Vivo Evidence and Possible Implications in Peritoneal Dialysis.

Author

Piccapane F, Gerbino A, Carmosino M, Milano S, Arduini A, Debellis L, Svelto M, Caroppo R, and Procino G

Subjects
Aquaporins genetics, Cell Line, Gene Expression Regulation genetics, Humans, Peritoneal Dialysis standards, Peritoneum pathology, Sodium metabolism, Aquaporin 1 genetics, Biological Transport genetics, Epithelium metabolism, Peritoneum metabolism
Abstract

We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA + dilution in the apical bathing solution, through TEA + -sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na + transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA + dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.

Published
2021
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39. β3 adrenergic receptor as potential therapeutic target in ADPKD.

Author

Schena G, Carmosino M, Chiurlia S, Onuchic L, Mastropasqua M, Maiorano E, Schena FP, and Caplan MJ

Subjects
Adrenergic beta-3 Receptor Antagonists pharmacology, Animals, Case-Control Studies, Cell Proliferation, Cells, Cultured, Epithelial Cells metabolism, Epithelial Cells pathology, Humans, Kidney metabolism, Kidney pathology, Male, Mice, Mice, Knockout, Polycystic Kidney, Autosomal Dominant etiology, Polycystic Kidney, Autosomal Dominant metabolism, Polycystic Kidney, Autosomal Dominant pathology, Cyclic AMP metabolism, Epithelial Cells drug effects, Kidney drug effects, Polycystic Kidney, Autosomal Dominant drug therapy, Propanolamines pharmacology, Receptors, Adrenergic, beta-3 chemistry
Abstract

Autosomal dominant polycystic kidney disease (ADPKD) disrupts renal parenchyma through progressive expansion of fluid-filled cysts. The only approved pharmacotherapy for ADKPD involves the blockade of the vasopressin type 2 receptor (V2R). V2R is a GPCR expressed by a subset of renal tubular cells and whose activation stimulates cyclic AMP (cAMP) accumulation, which is a major driver of cyst growth. The β3-adrenergic receptor (β3-AR) is a GPCR expressed in most segments of the murine nephron, where it modulates cAMP production. Since sympathetic nerve activity, which leads to activation of the β3-AR, is elevated in patients affected by ADPKD, we hypothesize that β3-AR might constitute a novel therapeutic target. We find that administration of the selective β3-AR antagonist SR59230A to an ADPKD mouse model (Pkd1 fl/fl ;Pax8 rtTA ;TetO-Cre) decreases cAMP levels, producing a significant reduction in kidney/body weight ratio and a partial improvement in kidney function. Furthermore, cystic mice show significantly higher β3-AR levels than healthy controls, suggesting a correlation between receptor expression and disease development. Finally, β3-AR is expressed in human renal tissue and localizes to cyst-lining epithelial cells in patients. Thus, β3-AR is a potentially interesting target for the development of new treatments for ADPKD., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Published
2021
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40. Activation of the Thiazide-Sensitive Sodium-Chloride Cotransporter by Beta3-Adrenoreceptor in the Distal Convoluted Tubule.

Author

Milano S, Carmosino M, Gerbino A, Saponara I, Lapi D, Dal Monte M, Bagnoli P, Svelto M, and Procino G

Abstract

We previously showed that the beta-3 adrenergic receptor (BAR3) is expressed in most segments of the nephron where its agonism promotes a potent antidiuretic effect. We localized BAR3 in distal convoluted tubule (DCT) cells expressing the thiazide-sensitive sodium-chloride cotransporter (NCC). Aim of this study is to investigate the possible functional role of BAR3 on NCC modulation in DCT cells. Here, we found that, in mice, the knockout of BAR3 was paralleled by a significant attenuation of NCC phosphorylation, paralleled by reduced expression and activation of STE-20/SPS1-related proline-alanine-rich kinase (SPAK) and WNKs the main kinases involved in NCC activation. Conversely, in BAR1/2 knockout mice, we found reduced NCC abundance with no changes in the phosphorylation state of NCC. Moreover, selective BAR3 agonism promotes both SPAK and NCC activation in wild-type mouse kidney slices. In conclusion, our findings suggest a novel role for BAR3 in the regulation of NCC in DCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Milano, Carmosino, Gerbino, Saponara, Lapi, Dal Monte, Bagnoli, Svelto and Procino.)

Published
2021
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41. Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration.

Author

Abruzzese V, Matera I, Martinelli F, Carmosino M, Koshal P, Milella L, Bisaccia F, and Ostuni A

Subjects
Actins metabolism, Cell Movement drug effects, Cell Survival drug effects, Drug Resistance, Multiple drug effects, Drug Resistance, Neoplasm drug effects, Gene Expression Regulation drug effects, Hep G2 Cells, Humans, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins genetics, Protein Multimerization drug effects, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Ion Channel Gating drug effects, Multidrug Resistance-Associated Proteins metabolism, Quercetin pharmacology
Abstract

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5'-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids.

Published
2021
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42. A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells.

Author

Piccapane F, Bonomini M, Castellano G, Gerbino A, Carmosino M, Svelto M, Arduini A, and Procino G

Subjects
Bicarbonates pharmacology, Biocompatible Materials, Cell Survival, Cytokines metabolism, Humans, Inflammation, Kidney Failure, Chronic, Microscopy, Confocal, Peritoneum drug effects, Tight Junctions metabolism, Ultrafiltration, Xylitol chemistry, Carnitine chemistry, Dialysis Solutions chemistry, Epithelium metabolism, Glucose metabolism, Peritoneal Dialysis methods
Abstract

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.

Published
2020
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44. Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka.

Author

Gerbino A, De Zio R, Russo D, Milella L, Milano S, Procino G, Pusch M, Svelto M, and Carmosino M

Subjects
Adenosine Triphosphate pharmacology, Animals, Cell Membrane drug effects, Cell Membrane metabolism, HEK293 Cells, Humans, Intravital Microscopy, Loop of Henle cytology, Male, Membrane Potentials drug effects, Mice, Microscopy, Confocal, Naphthalenes pharmacology, Patch-Clamp Techniques, Plant Extracts pharmacology, Plant Roots chemistry, Protein Kinase C antagonists & inhibitors, Signal Transduction drug effects, Taraxacum chemistry, Tetradecanoylphorbol Acetate pharmacology, Chloride Channels metabolism, Diuretics pharmacology, Loop of Henle metabolism, Protein Kinase C metabolism
Abstract

The physiological role of the renal ClC-Ka/ClC-K1 channels is to confer a high Cl - permeability to the thin Ascending Limb of Henle (tAL), which in turn is essential for establishing the high osmolarity of the renal medulla that drives water reabsorption from collecting ducts. Here, we investigated by whole-cell patch-clamp measurements on HEK293 cells co-expressing ClC-Ka (tagged with GFP) and the accessory subunit barttin (tagged with m-Cherry) the effect of a natural diuretic extract from roots of Dandelion (DRE), and other compounds activating PKC, such as ATP, on ClC-Ka activity and its membrane localization. Treatment with 400 µg/ml DRE significantly inhibited Cl - currents time-dependently within several minutes. Of note, the same effect on Cl - currents was obtained upon treatment with 100 µM ATP. Pretreatment of cells with either the intracellular Ca 2+ chelator BAPTA-AM (30 μM) or the PKC inhibitor Calphostin C (100 nM) reduced the inhibitory effect of DRE. Conversely, 1 µM of phorbol meristate acetate (PMA), a specific PKC activator, mimicked the inhibitory effect of DRE on ClC-Ka. Finally, we found that pretreatment with 30 µM Heclin, an E3 ubiquitin ligase inhibitor, did not revert DRE-induced Cl - current inhibition. In agreement with this, live-cell confocal analysis showed that DRE treatment did not induce ClC-Ka internalization. In conclusion, we demonstrate for the first time that the activity of ClC-Ka in renal cells could be significantly inhibited by the activation of PKC elicited by classical maneuvers, such as activation of purinergic receptors, or by exposure to herbal extracts that activates a PKC-dependent pathway. Overall, we provide both new information regarding the regulation of ClC-Ka and a proof-of-concept study for the use of DRE as new diuretic.

Published
2020
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45. Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway.

Author

Ostuni A, Carmosino M, Miglionico R, Abruzzese V, Martinelli F, Russo D, Laurenzana I, Petillo A, and Bisaccia F

Subjects
Adenosine Triphosphate metabolism, Cell Cycle drug effects, Cytoskeleton drug effects, Extracellular Space metabolism, Gene Expression Regulation, Neoplastic drug effects, Gene Silencing drug effects, Hep G2 Cells, Humans, Multidrug Resistance-Associated Proteins metabolism, Probenecid pharmacology, Cell Movement, Cytoskeleton metabolism, Multidrug Resistance-Associated Proteins antagonists & inhibitors, Purines metabolism
Abstract

ABCC6, belonging to sub-family C of ATP-binding cassette transporter, is an ATP-dependent transporter mainly present in the basolateral plasma membrane of hepatic and kidney cells. Although the substrates transported are still uncertain, ABCC6 has been shown to promote ATP release. The extracellular ATP and its derivatives di- and mono-nucleotides and adenosine by acting on specific receptors activate the so-called purinergic pathway, which in turn controls relevant cellular functions such as cell immunity, inflammation, and cancer. Here, we analyzed the effect of Abcc6 knockdown and probenecid-induced ABCC6 inhibition on cell cycle, cytoskeleton, and motility of HepG2 cells. Gene and protein expression were evaluated by quantitative Reverse Transcription PCR (RT-qPCR) and western blot, respectively. Cellular cycle analysis was evaluated by flow cytometry. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by in vitro wound-healing migration assay. Cell migration is reduced both in Abcc6 knockdown HepG2 cells and in probenecid treated HepG2 cells by interfering with the extracellular reserve of ATP. Therefore, ABCC6 could contribute to cytoskeleton rearrangements and cell motility through purinergic signaling. Altogether, our findings shed light on a new role of the ABCC6 transporter in HepG2 cells and suggest that its inhibitor/s could be considered potential anti-metastatic drugs.

Published
2020
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46. Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review.

Author

Faraone I, Sinisgalli C, Ostuni A, Armentano MF, Carmosino M, Milella L, Russo D, Labanca F, and Khan H

Subjects
Animals, Apoptosis drug effects, Cell Cycle Checkpoints drug effects, Humans, Neoplasms drug therapy, Xanthophylls pharmacology, Xanthophylls therapeutic use, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
Abstract

During the latest decades, the interest on the effectiveness of natural compounds and their impact on human health constantly increased, especially on those demonstrating to be effective on cancer. Molecules coming from nature are currently used in chemotherapy like Taxol, Vincristine or Vinblastine, and several other natural substances have been showed to be active in reducing cancer cell progression and migration. Among them, astaxanthin, a xanthophyll red colored carotenoid, displayed different biological activities including, antinflammatory, antioxidant, proapoptotic, and anticancer effects. It can induce apoptosis through downregulation of antiapoptotic protein (Bcl-2, p-Bad, and survivin) expression and upregulation of proapoptotic ones (Bax/Bad and PARP). Thanks to these mechanisms, it can exert anticancer effects towards colorectal cancer, melanoma, or gastric carcinoma cell lines. Moreover, it possesses antiproliferative activity in many experimental models and enhances the effectiveness of conventional chemotherapic drugs on tumor cells underling its potential future use. This review provides an overview of the current knowledge on the anticancer potential of astaxanthin by modulating several molecular targets. While it has been clearly demonstrated its multitarget activity in the prevention and regression of malignant cells in in vitro or in preclinical investigations, further clinical studies are needed to assess its real potential as anticancer in humans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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47. Functional study of a KCNH2 mutant: Novel insights on the pathogenesis of the LQT2 syndrome.

Author

De Zio R, Gerbino A, Forleo C, Pepe M, Milano S, Favale S, Procino G, Svelto M, and Carmosino M

Subjects
Adolescent, Adult, Cell Line, Cell Membrane genetics, Child, Electrocardiography methods, Female, HEK293 Cells, Humans, Male, Phenotype, Protein Transport genetics, Young Adult, ERG1 Potassium Channel genetics, Long QT Syndrome genetics, Long QT Syndrome pathology, Mutation genetics
Abstract

The K + voltage-gated channel subfamily H member 2 (KCNH2) transports the rapid component of the cardiac delayed rectifying K + current. The aim of this study was to characterize the biophysical properties of a C-terminus-truncated KCNH2 channel, G1006fs/49 causing long QT syndrome type II in heterozygous members of an Italian family. Mutant carriers underwent clinical workup, including 12-lead electrocardiogram, transthoracic echocardiography and 24-hour ECG recording. Electrophysiological experiments compared the biophysical properties of G1006fs/49 with those of KCNH2 both expressed either as homotetramers or as heterotetramers in HEK293 cells. Major findings of this work are as follows: (a) G1006fs/49 is functional at the plasma membrane even when co-expressed with KCNH2, (b) G1006fs/49 exerts a dominant-negative effect on KCNH2 conferring specific biophysical properties to the heterotetrameric channel such as a significant delay in the voltage-sensitive transition to the open state, faster kinetics of both inactivation and recovery from the inactivation and (c) the activation kinetics of the G1006fs/49 heterotetrameric channels is partially restored by a specific KCNH2 activator. The functional characterization of G1006fs/49 homo/heterotetramers provided crucial findings about the pathogenesis of LQTS type II in the mutant carriers, thus providing a new and potential pharmacological strategy., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Published
2019
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48. AQP1-Containing Exosomes in Peritoneal Dialysis Effluent As Biomarker of Dialysis Efficiency.

Author

Corciulo S, Nicoletti MC, Mastrofrancesco L, Milano S, Mastrodonato M, Carmosino M, Gerbino A, Corciulo R, Russo R, Svelto M, Gesualdo L, and Procino G

Subjects
Aged, Epithelial Cells cytology, Female, Humans, Male, Middle Aged, Peritoneal Dialysis methods, Aquaporin 1 urine, Biomarkers urine, Epithelial Cells metabolism
Abstract

The water channel Aquaporin 1 (AQP1) plays a fundamental role in water ultrafiltration during peritoneal dialysis (PD) and its reduced expression or function may be responsible for ultrafiltration failure (UFF). In humans, AQP1 is expressed in the endothelium of the peritoneal capillaries but its expression in mesothelial cells (MC) and its functional role in PD is still being debated. Here, we studied a cohort of 30 patients using PD in order to determine the presence of AQP1 in peritoneal biopsies, AQP1 release in the PD effluent through exosomes and the correlation of AQP1 abundance with the efficiency of peritoneal ultrafiltration. The experiments using immunofluorescence showed a strong expression of AQP1 in MCs. Immunoblotting analysis on vesicles isolated from PD effluents showed a consistent presence of AQP1, mesothelin and Alix and the absence of the CD31. Thus, this suggests that they have an exclusive mesothelial origin. The immunoTEM analysis showed a homogeneous population of nanovesicles and confirmed the immunoblotting results. Interestingly, the quantitative analysis by ELISA showed a positive correlation between AQP1 in the PD effluent and ultrafiltration (UF), free water transport (FWT) and Na-sieving. This evidence opens the discussion on the functional role of mesothelial AQP1 during PD and suggests that it may represent a potential non-invasive biomarker of peritoneal barrier integrity, with predictive potential of UFF in PD patients.

Published
2019
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49. Inhibiting the urokinase-type plasminogen activator receptor system recovers STZ-induced diabetic nephropathy.

Author

Dal Monte M, Cammalleri M, Pecci V, Carmosino M, Procino G, Pini A, De Rosa M, Pavone V, Svelto M, and Bagnoli P

Subjects
Animals, Diabetes Mellitus, Experimental chemically induced, Inflammation metabolism, Kidney metabolism, Male, Podocytes metabolism, Rats, Rats, Sprague-Dawley, Signal Transduction physiology, Up-Regulation physiology, Urokinase-Type Plasminogen Activator metabolism, Diabetes Mellitus, Experimental metabolism, Diabetic Nephropathies chemically induced, Diabetic Nephropathies metabolism, Receptors, Urokinase Plasminogen Activator metabolism, Streptozocin pharmacology
Abstract

The urokinase-type plasminogen activator (uPA) receptor (uPAR) participates to the mechanisms causing renal damage in response to hyperglycaemia. The main function of uPAR in podocytes (as well as soluble uPAR -(s)uPAR- from circulation) is to regulate podocyte function through αvβ3 integrin/Rac-1. We addressed the question of whether blocking the uPAR pathway with the small peptide UPARANT, which inhibits uPAR binding to the formyl peptide receptors (FPRs) can improve kidney lesions in a rat model of streptozotocin (STZ)-induced diabetes. The concentration of systemically administered UPARANT was measured in the plasma, in kidney and liver extracts and UPARANT effects on dysregulated uPAR pathway, αvβ3 integrin/Rac-1 activity, renal fibrosis and kidney morphology were determined. UPARANT was found to revert STZ-induced up-regulation of uPA levels and activity, while uPAR on podocytes and (s)uPAR were unaffected. In glomeruli, UPARANT inhibited FPR2 expression suggesting that the drug may act downstream uPAR, and recovered the increased activity of the αvβ3 integrin/Rac-1 pathway indicating a major role of uPAR in regulating podocyte function. At the functional level, UPARANT was shown to ameliorate: (a) the standard renal parameters, (b) the vascular permeability, (c) the renal inflammation, (d) the renal fibrosis including dysregulated plasminogen-plasmin system, extracellular matrix accumulation and glomerular fibrotic areas and (e) morphological alterations of the glomerulus including diseased filtration barrier. These results provide the first demonstration that blocking the uPAR pathway can improve diabetic kidney lesion in the STZ model, thus suggesting the uPA/uPAR system as a promising target for the development of novel uPAR-targeting approaches., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Published
2019
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50. Role of Lamin A/C Gene Mutations in the Signaling Defects Leading to Cardiomyopathies.

Author

Gerbino A, Procino G, Svelto M, and Carmosino M

Abstract

Nuclear lamin A/C are crucial components of the intricate protein mesh that underlies the inner nuclear membrane and confers mainly nuclear and cytosolic rigidity. However, throughout the years a number of other key physiological processes have been associated with lamins such as modulation of both genes expression and the activity of signaling mediators. To further solidify its importance in cell physiology, mutations in the lamin A/C gene ( LMNA ) have been associated to diverse pathological phenotypes with skeletal muscles and the heart being the most affected systems. When affected, the heart develops a wide array of phenotypes spanning from dilated cardiomyopathy with conduction defects to arrhythmogenic right ventricular cardiomyopathy. The surprising large number of cardiac phenotypes reflects the equally large number of specific mutations identified in the LMNA gene. In this review, we underlie how mutations in LMNA can impact the activity and the spatial/temporal organization of signaling mediators and transcription factors. We analyzed the ever-increasing amount of findings collected in Lmna H222P/H222P mice whose cardiomyopathy resemble the most important features of the disease in humans and a number of key evidences from other experimental models. With this mini review, we attempt to combine the newest insights regarding both the pathogenic effects of LMNA mutations in terms of signaling abnormalities and cardiac laminopathies.

Published
2018
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