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10. Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD

Author

Park, Frank, Sweeney, William E., Jr., Jia, Guangfu, Akbulut, Talha, Mueller, Benjamin, Falck, J. Russell, Birudaraju, Saritha, Roman, Richard J., and Avner, Ellis D.

Subjects
Polycystic kidney disease -- Development and progression, Cytochrome P-450 -- Properties, Epithelial cells -- Properties, Cell proliferation -- Research, Biological sciences
Abstract

20-Hydroxyeicosatetraenoic acid (20-HETE) has been implicated as a potential mediator in epithelial cell proliferation and cyst formation in polycystic kidney disease (PKD). In the present study, we studied the effects of chronic blockade of 20-HETE synthesis in an orthologous rodent model of autosomal recessive polycystic kidney disease (ARPKD), the PCK rat. RT-PCR analysis indicated that the expression of CYP4A1, CYP4A2, CYP4A3, and CYP4A8 mRNA was increased two- to fourfold in cystic PCK compared with noncystic Sprague-Dawley rat kidneys. Daily administration of a 20-HETE synthesis inhibitor, HET-0016 (10 mg x [kg.sup.-1] x [day.sup.-1] ip) for 4-7 wk significantly reduced kidney size by 24% from 4.95 [+ or -] 0.19 g in vehicle-treated PCK rats to 3.76 [+ or -] 0.15 g (n = 4). Collecting tubule morphometric cystic indices were reduced in HET-0016-treated PCK rats (2.1 [+ or -] 0.2; n = 4) compared with vehicle-treated PCK rats (4.4 [+ or -] 0.1; n = 4). The cellular mechanism by which 20-HETE may play a role in cyst formation has not been well characterized, but there was a significantly lower (P < 0.05) level of intracellular cAMP and decreased phosphorylation (activation) of ERK1/2 protein in PCK rat kidneys (n = 3) treated with HET-0016 . These studies indicate a potential role of 20-HETE in cyst formation in the orthologous rodent PCK model of ARPKD. cytochrome P-450; HET-0016; epithelial cell proliferation; polycystic kidney rat; pck; autosomal recessive polycystic kidney mouse

Published
2009

11. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration

Author

Kermorvant-Duchemin, Elsa, Sennlaub, Florian, Sirinyan, Mirna, Brault, Sonia, Andelfinger, Gregor, Kooli, Amna, Germain, Stephane, Ong, Huy, d'Orleans-Juste, Pedro, Gobeil, Fernand, Jr, Zhu, Tang, Boisvert, Chantal, Hardy, Pierre, Jain, Kavita, Falck, J Russel, Balazy, Michael, and Chemtob, Sylvain

Abstract

Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO[sub.2][sup.*]-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO[sup.*]-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies., Author(s): Elsa Kermorvant-Duchemin [1, 9]; Florian Sennlaub [1, 2, 9]; Mirna Sirinyan [1, 3]; Sonia Brault [1, 3]; Gregor Andelfinger [1]; Amna Kooli [1, 3]; Stephane Germain [4]; Huy Ong [...]

Published
2005
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17. Epoxyeicosatrienoic intervention improves NAFLD in leptin receptor deficient mice by an increase in PGC1α-HO-1-PGC1α-mitochondrial signaling

Author

Raffaele, M., Bellner, L., Singh, S. P., Favero, G., Rezzani, R., Rodella, L. F., Falck, J. R., Abraham, N. G., and Vanella, L.

Subjects
CYP-450 epoxygenase, Insulin sensitivity, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mitochondria, Non-alcoholic fatty liver disease (NAFLD), Fatty Liver, Disease Models, Animal, Mice, FGF21, SIRT1, 8,11,14-Eicosatrienoic Acid, Non-alcoholic Fatty Liver Disease, Animals, Receptors, Leptin, Heme Oxygenase-1, Signal Transduction
Abstract

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and is considered to be an inflammatory disorder characterized by fatty acid accumulation, oxidative stress, and lipotoxicity. We have previously reported that epoxyeicosatrienoic acid-agonist (EET-A) has multiple beneficial effects on cardiac, renal and adipose tissue function while exhibiting both anti-inflammatory and anti-oxidant activities. We hypothesized that EET-A intervention would play a central role in attenuation of obesity-induced steatosis and hepatic fibrosis that leads to NAFLD.We studied the effect of EET-A on fatty liver using db/db mice as a model of obesity. Mice were fed a high fat diet (HFD) for 16 weeks and administered EET-A twice weekly for the final 8 weeks.db/db mice fed HFD significantly increased hepatic lipid accumulation as manifested by increases in NAS scores, hepatic fibrosis, insulin resistance, and inflammation, and decreases in mitochondrial mitofusin proteins (Mfn 1/2) and anti-obesity genes Fibroblast growth factor 21 (FGF21) and Cellular Repressor of E1A-Stimulated Genes 1 (CREG1). EET-A administration reversed the decrease in these genes and reduced liver fibrosis. Knockout of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in EET-A treated mice resulted in a reversal of the beneficial effects of EET-A administration.EET-A intervention diminishes fatty acid accumulation, fibrosis, and NFALD associated with an increase in HO-1-PGC1α and increased insulin receptor phosphorylation. A pharmacological strategy involving EETs may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NAFLD.

Published
2019

18. The Forest Observation System, building a global reference dataset for remote sensing of forest biomass [data paper]

Author

Schepaschenko, D., Chave, J., Phillips, O. L., Lewis, S. L., Davies, S. J., Réjou-Méchain, Maxime, Sist, P., Scipal, K., Perger, C., Herault, B., Labriere, N., Hofhansl, F., Affum-Baffoe, K., Aleinikov, A., Alonso, A., Amani, C., Araujo-Murakami, A., Armston, J., Arroyo, L., Ascarrunz, N., Azevedo, C., Baker, T., Balazy, R., Bedeau, C., Berry, N., Bilous, A. M., Bilous, S. Y., Bissiengou, P., Blanc, L., Bobkova, K. S., Braslavskaya, T., Brienen, R., Burslem, Dfrp, Condit, R., Cuni-Sanchez, A., Danilina, D., Torres, D. D., Derroire, G., Descroix, L., Sotta, E. D., d'Oliveira, M. V. N., Dresel, C., Erwin, T., Evdokimenko, M. D., Falck, J., Feldpausch, T. R., Foli, E. G., Foster, R., Fritz, S., Garcia-Abril, A. D., Gornov, A., Gornova, M., Gothard-Bassebe, E., Gourlet-Fleury, S., Guedes, M., Hamer, K. C., Susanty, F. H., Higuchi, N., Coronado, E. N. H., Hubau, W., Hubbell, S., Ilstedt, U., Ivanov, V. V., Kanashiro, M., Karlsson, A., Karminov, V. N., Killeen, T., Koffi, J. C. K., Konovalova, M., Kraxner, F., Krejza, J., Krisnawati, H., Krivobokov, L. V., Kuznetsov, M. A., Lakyda, I., Lakyda, P. I., Licona, J. C., Lucas, R. M., Lukina, N., Lussetti, D., Malhi, Y., Manzanera, J. A., Marimon, B., Martinez, R. V., Martynenko, O. V., Matsala, M., Matyashuk, R. K., Mazzei, L., Memiaghe, H., Mendoza, C., Mendoza, A. M., Moroziuk, O. V., Mukhortova, L., Musa, S., Nazimova, D. I., Okuda, T., Oliveira, L. C., Ontikov, P. V., Osipov, A. F., Pietsch, S., Playfair, M., Poulsen, J., Radchenko, V. G., Rodney, K., Rozak, A. H., Ruschel, A., Rutishauser, E., See, L., Shchepashchenko, M., Shevchenko, N., Shvidenko, A., Silveira, M., Singh, J., Sonke, B., Souza, C., Sterenczak, K., Stonozhenko, L., Sullivan, M. J. P., Szatniewska, J., Aedoumg, H. T., Ter Steege, H., Tikhonova, E., Toledo, M., Trefilova, O. V., Valbuena, R., Gamarra, L. V., Vasiliev, S., Vedrova, E. F., Verhovets, S. V., Vidal, E., Vladimirova, N. A., Vleminckx, J., Vos, V. A., Vozmitel, F. K., Wanek, W., West, T. A. P., Woell, H., Woods, J. T., Wortel, V., Yamada, T., Hajar, Z. S. N., and Zo-Bi, I. C.

Abstract

Forest biomass is an essential indicator for monitoring the Earth's ecosystems and climate. It is a critical input to greenhouse gas accounting, estimation of carbon losses and forest degradation, assessment of renewable energy potential, and for developing climate change mitigation policies such as REDD+, among others. Wall-to-wall mapping of aboveground biomass (AGB) is now possible with satellite remote sensing (RS). However, RS methods require extant, up-to-date, reliable, representative and comparable in situ data for calibration and validation. Here, we present the Forest Observation System (FOS) initiative, an international cooperation to establish and maintain a global in situ forest biomass database. AGB and canopy height estimates with their associated uncertainties are derived at a 0.25 ha scale from field measurements made in permanent research plots across the world's forests. All plot estimates are geolocated and have a size that allows for direct comparison with many RS measurements. The FOS offers the potential to improve the accuracy of RS- based biomass products while developing new synergies between the RS and ground-based ecosystem research communities.

Published
2019

21. A global reference dataset for remote sensing of forest biomass. The Forest Observation System approach

Author

Shchepashchenko, D., Chave, J., Phillips, O.L., Lewis, S.L., Davies, S.J., Réjou-Méchain, M., Sist, P., Scipal, K., Perger, C., Herault, B., Labrière, N., Hofhansl, F., Affum-Baffoe, K., Aleinikov, A., Alonso, A., Amani, C., Araujo-Murakami, A., Armston, J., Arroyo, L., Ascarrunz, N., Azevedo, C., Baker, T., Bałazy, R., Banki, O., Bedeau, C., Berry, N., Bilous, A.M., Bilous, S.Y., Bissiengou, P., Blanc, L., Bobkova, K.S., Braslavskaya, T., Brienen, R., Burslem, D., Condit, R., Cuni-Sanchez, A., Danilina, D., del Castillo Torres, D., Derroire, G., Descroix, L., Doff Sotta, E., d'Oliveira, M.V.N., Dresel, C., Erwin, T., Evdokimenko, M.D., Falck, J., Feldpausch, T.R., Foli, E.G., Foster, R., Fritz, S., Garcia-Abril, A.D., Gornov, A., Gornova, M., Gothard-Bassébé, E., Gourlet-Fleury, S., Guedes, M., Hamer, K., Susanty, F.H., Higuchi, N., Honorio Coronado, E.N., Hubau, W., Hubbell, S., Ilstedt, U., Ivanov, V., Kanashiro, M., Karlsson, A., Karminov, V.N., Killeen, T., Konan, J.K., Konovalova, M., Kraxner, F., Krejza, J., Krisnawati, H., Krivobokov, L.V., Kuznetsov, M.A., Lakyda, I., Lakyda, P.I., Licona, J.C., Lucas, R.M., Lukina, N., Lussetti, D., Malhi, Y., Manzanera, J.A., Marimon, B., Marimon Junior, B.H., Martinez, R.V., Martynenko, O.V., Matsala, M.S., Matyashuk, R.K., Mazzei, L., Memiaghe, H., Mendoza, C., Monteagudo-Mendoza, A., Morozyuk, O.V., Mukhortova, L., Musa, S., Nazimova, D.I., Okuda, T., Oliveira, L.C., Ontikov, P.V., Osipov, A.F., Gutierrez, A.P., Pietsch, S., Playfair, M., Poulsen, J., Radchenko, V., Rodney, K., Rozak, A.H., Ruschel, A., Rutishauser, E., See, L., Shchepashchenko, M., Shevchenko, N., Shvidenko, A., Silva-Espejo, J.E., Silveira, M., Singh, J., Sonké, B., Souza, C., Stereńczak, K., Sullivan, M.J.P., Szatniewska, J., Taedoumg, H., ter Steege, H., Tikhonova, E., Toledo, M., Trefilova, O.V., Valbuena, R., Valenzuela Gamarra, L.V., Vedrova, E.F., Verhovets, S.V., Vidal, E., Vladimirova, N.A., Vleminckx, J., Vos, V.A., Vozmitel, F.K., Wanek, W., West, T.A.P., Woell, H., Woods, J.T., Wortel, V., Yamada, T., Zamah Shari, N.H., Zo-Bi, I.C., Shchepashchenko, D., Chave, J., Phillips, O.L., Lewis, S.L., Davies, S.J., Réjou-Méchain, M., Sist, P., Scipal, K., Perger, C., Herault, B., Labrière, N., Hofhansl, F., Affum-Baffoe, K., Aleinikov, A., Alonso, A., Amani, C., Araujo-Murakami, A., Armston, J., Arroyo, L., Ascarrunz, N., Azevedo, C., Baker, T., Bałazy, R., Banki, O., Bedeau, C., Berry, N., Bilous, A.M., Bilous, S.Y., Bissiengou, P., Blanc, L., Bobkova, K.S., Braslavskaya, T., Brienen, R., Burslem, D., Condit, R., Cuni-Sanchez, A., Danilina, D., del Castillo Torres, D., Derroire, G., Descroix, L., Doff Sotta, E., d'Oliveira, M.V.N., Dresel, C., Erwin, T., Evdokimenko, M.D., Falck, J., Feldpausch, T.R., Foli, E.G., Foster, R., Fritz, S., Garcia-Abril, A.D., Gornov, A., Gornova, M., Gothard-Bassébé, E., Gourlet-Fleury, S., Guedes, M., Hamer, K., Susanty, F.H., Higuchi, N., Honorio Coronado, E.N., Hubau, W., Hubbell, S., Ilstedt, U., Ivanov, V., Kanashiro, M., Karlsson, A., Karminov, V.N., Killeen, T., Konan, J.K., Konovalova, M., Kraxner, F., Krejza, J., Krisnawati, H., Krivobokov, L.V., Kuznetsov, M.A., Lakyda, I., Lakyda, P.I., Licona, J.C., Lucas, R.M., Lukina, N., Lussetti, D., Malhi, Y., Manzanera, J.A., Marimon, B., Marimon Junior, B.H., Martinez, R.V., Martynenko, O.V., Matsala, M.S., Matyashuk, R.K., Mazzei, L., Memiaghe, H., Mendoza, C., Monteagudo-Mendoza, A., Morozyuk, O.V., Mukhortova, L., Musa, S., Nazimova, D.I., Okuda, T., Oliveira, L.C., Ontikov, P.V., Osipov, A.F., Gutierrez, A.P., Pietsch, S., Playfair, M., Poulsen, J., Radchenko, V., Rodney, K., Rozak, A.H., Ruschel, A., Rutishauser, E., See, L., Shchepashchenko, M., Shevchenko, N., Shvidenko, A., Silva-Espejo, J.E., Silveira, M., Singh, J., Sonké, B., Souza, C., Stereńczak, K., Sullivan, M.J.P., Szatniewska, J., Taedoumg, H., ter Steege, H., Tikhonova, E., Toledo, M., Trefilova, O.V., Valbuena, R., Valenzuela Gamarra, L.V., Vedrova, E.F., Verhovets, S.V., Vidal, E., Vladimirova, N.A., Vleminckx, J., Vos, V.A., Vozmitel, F.K., Wanek, W., West, T.A.P., Woell, H., Woods, J.T., Wortel, V., Yamada, T., Zamah Shari, N.H., and Zo-Bi, I.C.

Abstract

Forest biomass is an essential indicator for monitoring the Earth’s ecosystems and climate. It is a critical input to greenhouse gas accounting, estimation of carbon losses and forest degradation, assessment of renewable energy potential, and for developing climate change mitigation policies such as REDD+, among others. Wall-to-wall mapping of aboveground biomass (AGB) is now possible with satellite remote sensing (RS). However, RS methods require extant, up-to-date, reliable, representative and comparable in situ data for calibration and validation. Here, we present the Forest Observation System (FOS) initiative, an international cooperation to establish and maintain a global in situ forest biomass database. AGB and canopy height estimates with their associated uncertainties are derived at a 0.25ha scale from field measurements made in permanent research plots across the world's forests. All plot estimates are geolocated and have a size that allows for direct comparison with many RS measurements. The FOS offers the potential to improve the accuracy of RS-based biomass products while developing new synergies between the RS and ground-based ecosystem research communities. Live, most up-to-date dataset is available at https://forest-observation-system.net

Published
2019

22. The Forest Observation System, building a global reference dataset for remote sensing of forest biomass

Author

Schepaschenko, D., Chave, J., Phillips, O.L., Lewis, S.L., Davies, S.J., Réjou-Méchain, M., Sist, P., Scipal, K., Perger, C., Herault, B., Labrière, N., Hofhansl, F., Affum-Baffoe, K., Aleinikov, A., Alonso, A., Amani, C., Araujo-Murakami, A., Armston, J., Arroyo, L., Ascarrunz, N., Azevedo, C., Baker, T., Bałazy, R., Bedeau, C., Berry, N., Bilous, A.M., Bilous, S., Bissiengou, P., Blanc, L., Bobkova, .S., Braslavskaya, T., Brienen, R., Burslem, D., Condit, R., Cuni-Sanchez, A., Danilina, D., del Castillo Torres, D., Derroire, G., Descroix, L., Sotta, E.D., d’Oliveira, M.V.N., Dresel, C., Erwin, T., Evdokimenko, M.D., Falck, J., Feldpausch, T.R., Foli, E.G., Foster, R., Fritz, S., Garcia-Abril, A.D., Gornov, A., Gornova, M., Gothard-Bassébé, E., Gourlet-Fleury, S., Guedes, M., Hamer, K.C., Susanty, F.H., Higuchi, N., Coronado, E.N.H., Hubau, W., Hubbell, S., Ilstedt, U., Ivanov, V.V., Kanashiro, M., Karlsson, A., Karminov, V.N., Killeen, T., Koffi, J.-C., Konovalova, M., Kraxner, F., Krejza, J., Krisnawati, H., Krivobokov, L.V., Kuznetsov, M.A., Lakyda, I., Lakyda, P.I., Licona, J.C., Lucas, R.M., Lukina, N., Lussetti, D., Malhi, Y., Manzanera, J.A., Marimon, B., Marimon, B.H., Martinez, R.V., Martynenko, O.V., Matsala, M., Matyashuk, R.K., Mazzei, L., Memiaghe, H., Mendoza, C., Mendoza, A.M., Moroziuk, Olga V., Mukhortova, L., Musa, S., Nazimova, D.I., Okuda, T., Oliveira, L.C., Ontikov, P.V., Osipov, A., Pietsch, S., Playfair, M., Poulsen, J., Radchenko, V.G., Rodney, K., Rozak, A.H., Ruschel, A., Rutishauser, E., See, L., Shchepashchenko, M., Shevchenko, N., Shvidenko, A., Silveira, M., Singh, J., Sonké, B., Souza, C., Stereńczak, K., Stonozhenko, L., Sullivan, M., Szatniewska, J., Taedoumg, H., ter Steege, H., Tikhonova, E., Toledo, M., Trefilova, O.V., Valbuena, R., Gamarra, L.V., Vasiliev, S., Vedrova, E.F., Verhovets, S.V., Vidal, E., Vladimirova, N.A., Vleminckx, J., Vos, V.A., Vozmitel, F.K., Wanek, W., West, T., Woell, H., Woods, J.T., Wortel, V., Yamada, T., Nur Hajar, Z., Zo-Bi, I., Schepaschenko, D., Chave, J., Phillips, O.L., Lewis, S.L., Davies, S.J., Réjou-Méchain, M., Sist, P., Scipal, K., Perger, C., Herault, B., Labrière, N., Hofhansl, F., Affum-Baffoe, K., Aleinikov, A., Alonso, A., Amani, C., Araujo-Murakami, A., Armston, J., Arroyo, L., Ascarrunz, N., Azevedo, C., Baker, T., Bałazy, R., Bedeau, C., Berry, N., Bilous, A.M., Bilous, S., Bissiengou, P., Blanc, L., Bobkova, .S., Braslavskaya, T., Brienen, R., Burslem, D., Condit, R., Cuni-Sanchez, A., Danilina, D., del Castillo Torres, D., Derroire, G., Descroix, L., Sotta, E.D., d’Oliveira, M.V.N., Dresel, C., Erwin, T., Evdokimenko, M.D., Falck, J., Feldpausch, T.R., Foli, E.G., Foster, R., Fritz, S., Garcia-Abril, A.D., Gornov, A., Gornova, M., Gothard-Bassébé, E., Gourlet-Fleury, S., Guedes, M., Hamer, K.C., Susanty, F.H., Higuchi, N., Coronado, E.N.H., Hubau, W., Hubbell, S., Ilstedt, U., Ivanov, V.V., Kanashiro, M., Karlsson, A., Karminov, V.N., Killeen, T., Koffi, J.-C., Konovalova, M., Kraxner, F., Krejza, J., Krisnawati, H., Krivobokov, L.V., Kuznetsov, M.A., Lakyda, I., Lakyda, P.I., Licona, J.C., Lucas, R.M., Lukina, N., Lussetti, D., Malhi, Y., Manzanera, J.A., Marimon, B., Marimon, B.H., Martinez, R.V., Martynenko, O.V., Matsala, M., Matyashuk, R.K., Mazzei, L., Memiaghe, H., Mendoza, C., Mendoza, A.M., Moroziuk, Olga V., Mukhortova, L., Musa, S., Nazimova, D.I., Okuda, T., Oliveira, L.C., Ontikov, P.V., Osipov, A., Pietsch, S., Playfair, M., Poulsen, J., Radchenko, V.G., Rodney, K., Rozak, A.H., Ruschel, A., Rutishauser, E., See, L., Shchepashchenko, M., Shevchenko, N., Shvidenko, A., Silveira, M., Singh, J., Sonké, B., Souza, C., Stereńczak, K., Stonozhenko, L., Sullivan, M., Szatniewska, J., Taedoumg, H., ter Steege, H., Tikhonova, E., Toledo, M., Trefilova, O.V., Valbuena, R., Gamarra, L.V., Vasiliev, S., Vedrova, E.F., Verhovets, S.V., Vidal, E., Vladimirova, N.A., Vleminckx, J., Vos, V.A., Vozmitel, F.K., Wanek, W., West, T., Woell, H., Woods, J.T., Wortel, V., Yamada, T., Nur Hajar, Z., and Zo-Bi, I.

Abstract

Forest biomass is an essential indicator for monitoring the Earth’s ecosystems and climate. It is a critical input to greenhouse gas accounting, estimation of carbon losses and forest degradation, assessment of renewable energy potential, and for developing climate change mitigation policies such as REDD+, among others. Wall-to-wall mapping of aboveground biomass (AGB) is now possible with satellite remote sensing (RS). However, RS methods require extant, up-to-date, reliable, representative and comparable in situ data for calibration and validation. Here, we present the Forest Observation System (FOS) initiative, an international cooperation to establish and maintain a global in situ forest biomass database. AGB and canopy height estimates with their associated uncertainties are derived at a 0.25 ha scale from field measurements made in permanent research plots across the world’s forests. All plot estimates are geolocated and have a size that allows for direct comparison with many RS measurements. The FOS offers the potential to improve the accuracy of RS-based biomass products while developing new synergies between the RS and ground-based ecosystem research communities.

Published
2019

25. Characterization of cytochrome P-450-dependent arachidonic acid metabolism in rabbit intestine

Author

Macica, Carolyn, Balazy, Michael, Falck, J. R., Mioskowski, Charles, and Carroll, Mairead A.

Subjects
Cytochrome P-450 -- Physiological aspects, Arachidonic acid -- Physiological aspects, Intestines -- Physiological aspects, Biological sciences
Abstract

Arachidonate (P-450-AA) metabolism which relies on cytochrome P-450 in the entire intestinal tract was characterized because epithelial ion movement and regional blood flow are altered by a few metabolites obtained from this pathway. Regional differences are displayed by P-450-AA metabolism in its dispersal in the entire small, large and transverse rabbit intestines. The ileum contained the maximum activity of P-450 metabolism. Omega and subterminal monohydroxyeicosatetraenoic acids were the main P-450-AA metabolites produced by ideal microsomers.

Published
1993

30. Bromo-boronolactonization of olefins

Author

Falck, J. R., Bondlela, Muralidhar, Venkataraman, Sylesh K., and Srinivas, Dale

Subjects
Chemistry, Organic -- Research, Olefins -- Physiological aspects, Bromine -- Physiological aspects, Boron -- Physiological aspects, Hydrogen -- Physiological aspects, Oxygen -- Physiological aspects, Acids -- Physiological aspects, Nitrogen -- Physiological aspects, Biological sciences, Chemistry
Abstract

Research has been conducted on the mono- and disubstituted ortho-alkenylarylboronic acids. The facile formation of the bromo-boronolactones by the ortho-alkenylarylboronic acids exposure to N-bromosuccinimide in tetrahydrofuran/H (sub)2 O has been investigated and the results are presented.

Published
2001

33. Intramolecular Mitsunobu displacement with carbon nucleophiles: preparation of alpha-nitrocyclopropanes

Author

Jurong Yu, Falck, J. R., and Mioskowski, Charles

Subjects
Organic compounds -- Synthesis, Nitrogen compounds -- Research, Gases -- Usage, Azo compounds -- Usage, Substitution reactions -- Research, Cyclopropane compounds -- Research, Biological sciences, Chemistry
Abstract

The preformed complex diethyl azodicarboxylate/triphenylphosphine (DEAD/Ph3P) allows efficient synthesis of alpha-nitrocylopropanes. The process involves treating gamma-nitroalkanols with DEAD/Ph3P at room temperature under neutral conditions in benzene or tetrahydrofuran. A modified Mitsunobu displacement takes place, whereby the nitronate anion serves as a carbon nucleophile, and results in a new carbon-carbon bond. The cycloproducts are formed in 64-98% yields. The reactions favor the formation of trans products due to kinetic rather than thermodynamic factors.

Published
1992

35. Development of a Primary Human Co-Culture Model of Inflamed Airway Mucosa

Author

Yonker, Lael M., primary, Mou, Hongmei, additional, Chu, Kengyeh K., additional, Pazos, Michael A., additional, Leung, Huimin, additional, Cui, Dongyao, additional, Ryu, Jinhyeob, additional, Hibbler, Rhianna M., additional, Eaton, Alexander D., additional, Ford, Tim N., additional, Falck, J. R., additional, Kinane, T. Bernard, additional, Tearney, Guillermo J., additional, Rajagopal, Jayaraj, additional, and Hurley, Bryan P., additional

Published
2017
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36. Vasodilatory Responses of Renal Interlobular Arteries to Epoxyeicosatrienoic Acids Analog Are Not Enhanced in Ren-2 Transgenic Hypertensive Rats: Evidence Against a Role of Direct Vascular Effects of Epoxyeicosatrienoic Acids in Progression of Experimental Heart Failure

Author

SPORKOVÁ, A., primary, HUSKOVÁ, Z., additional, ŠKAROUPKOVÁ, P., additional, RAMI REDDY, N., additional, FALCK, J. R., additional, SADOWSKI, J., additional, and ČERVENKA, L., additional

Published
2017
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37. A one-pot synthesis of pyrido[2,3-b][1,4]oxazin-2-ones

Author

Su-Dong Cho, Yong-Dae Park, Jeum-Jong Kim, Sang-Gyeong Lee, Chen Ma, Sang-Yong Song, Woo-Hong Joo, Falck, J. R., Shiro, Motoo, Dong-Soo Shin, and Yong-Jin Yoon

Subjects
Acetonitrile -- Chemical properties, Carbonates -- Chemical properties, Cesium -- Chemical properties, Chemistry, Organic -- Research, Hydrogen -- Chemical properties, Nitrogen -- Chemical properties, Organic compounds -- Chemical properties, Organic compounds -- Composition, Oxo compounds -- Chemical properties, Oxo compounds -- Composition, Pyridine -- Chemical properties, Substitution reactions -- Analysis, Biological sciences, Chemistry
Abstract

Research has been conducted on pyrido[2,3-b][1,4]oxazin-2-ones. The authors describe the preparation of these compounds via one-pot annulation of N-substituted-2-chloroacetamides with 2-halo-3-hydroxypyridines using cesium carbonate in refluxing acetonitrile.

Published
2003

38. Chemical and electrical properties of interfaces between deposited insulators and La2CuO4.

Author

Levy, A., Lercel, M. J., Falck, J. P., Kastner, M. A., Bright, A. A., and Kleinsasser, A. W.

Subjects
SILICON nitride, SILICA, LANTHANUM compounds, SEMICONDUCTORS
Abstract

Focuses on a study which characterized the insulator and semiconductor interfaces between deposited insulators silicon nitride and silicon dioxide on lanthanum cuprate semiconducting single crystals. Description of the fabrication of metal-insulator-semiconductor capacitors; Observations on copper and oxygen behavior; Comparison of stability between the insulators.

Published
1992
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39. CTCF-mediated chromatin loops enclose inducible gene regulatory domains

Author

Oti, M.O., Falck, J., Huynen, M.A., Zhou, Huiqing, Oti, M.O., Falck, J., Huynen, M.A., and Zhou, Huiqing

Abstract

Contains fulltext : 172060.pdf (publisher's version ) (Open Access), BACKGROUND: The CCTC-binding factor (CTCF) protein is involved in genome organization, including mediating three-dimensional chromatin interactions. Human patient lymphocytes with mutations in a single copy of the CTCF gene have reduced expression of enhancer-associated genes involved in response to stimuli. We hypothesize that CTCF interactions stabilize enhancer-promoter chromatin interaction domains, facilitating increased expression of genes in response to stimuli. Here we systematically investigate this model using computational analyses. RESULTS: We use CTCF ChIA-PET data from the ENCODE project to show that CTCF-associated chromatin loops have a tendency to enclose regions of enhancer-regulated stimulus responsive genes, insulating them from neighboring regions of constitutively expressed housekeeping genes. To facilitate cell type-specific CTCF loop identification, we develop an algorithm to predict CTCF loops from ChIP-seq data alone by exploiting the CTCF motif directionality in loop anchors. We apply this algorithm to a hundred ENCODE cell line datasets, confirming the universality of our observations as well as identifying a general distinction between primary and immortal cells in loop-enclosed gene content. Finally, we combine the existing evidence to propose a model for the formation of CTCF loops in which partner sites are brought together by chromatin template reeling through stationary RNA polymerases, consistent with the transcription factory hypothesis. CONCLUSIONS: We provide computational evidence that CTCF-mediated chromatin interactions enclose domains of stimulus responsive enhancer-regulated genes, insulating them from nearby housekeeping genes.

Published
2016

40. Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport

Author

QUIGLEY, RAYMOND, BAUM, MICHEL, REDDY, KOMANDLA MALLA, GRIENER, JAMES C., and FALCK, J. R.

Subjects
Kidney tubules -- Physiological aspects, Cytochrome P-450 -- Physiological aspects, Biological transport -- Research, Kidneys -- Physiological aspects, Biological sciences
Abstract

Quigley, Raymond, Michel Baum, Komandla Malla Reddy, James C. Griener, and J. R. Falck. Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport. Am J Physiol Renal Physiol 278: F949-F953, 2000.--The kidney has the highest abundance of cytochrome P-450 of all extrahepatic organs. Within the kidney, the highest concentration of cytochrome P-450 is found in the proximal tubule. Whether 20- or 19(S)-hydroxyeicosatetraenoic acid (HETE), the major P-450 metabolites of arachidonic acid in the proximal tubule, affect transport in this segment has not been previously investigated. We examined the direct effects of 20- and 19(S)-HETE on volume absorption ([J.sub.v]) in the rabbit proximal straight tubule (PST). Production of 20-HETE by rabbit PST was demonstrated by incubating microdissected tubules with [[sup.3]H]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [[sup.3]H]arachidonic acid to 20-HETE in control tubules that was inhibited by [10.sup.-5] M N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). Addition of exogenous 20-HETE had no effect on PST volume transport. However, inhibition of endogenous production of 20-HETE using DDMS stimulated transport. In the presence of DDMS, 20-HETE inhibited PST [J.sub.v]. 19(S)-HETE in the bathing solution stimulated PST [J.sub.v] alone and in the presence of DDMS. Thus [Omega]- and [Omega]-1-hydroxylase products of arachidonic acid have direct effects on PST transport. Endogenous production of 20-HETE may play a role in tonic suppression of transport and may therefore be an endogenous regulator of transport in the proximal tubule. in vitro microperfusion; cytochrome P-450; [Omega]-hydroxylase; hypertension; sodium-potassium-adenosinetriphosphatase; hydroxyeicosatetraenoic acids

Published
2000

43. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice

Author

Panigrahy, D, Edin, M L, Lee, C R, Huang, S, Bielenberg, D R, Butterfield, C E, Barnés, C M, Mammoto, A, Mammoto, T, Luria, A, Benny, O, Chaponis, D M, Dudley, A C, Greene, E R, Vergilio, J A, Pietramaggiori, G, Scherer-Pietramaggiori, S S, Short, S M, Seth, M, Lih, F B, Tomer, K B, Yang, J, Schwendener, R A, Hammock, B D, Falck, J R, Manthati, V L, Ingber, D E, Kaipainen, A, D'Amore, P A, Kieran, M W, Zeldin, D C, University of Zurich, and Panigrahy, D

Subjects
10061 Institute of Molecular Cancer Research, cardiovascular system, 570 Life sciences, biology, lipids (amino acids, peptides, and proteins), 2700 General Medicine
Abstract

Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.

Published
2012
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49. Reactivity of g-chloro-gem-trichloro alkanes with chromous chloride

Author

Tisserand, Stephane, Bejot, R., Billaud, C., Li De Run, R., Falck, J. R., Mioskowski, C., Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Erhart, Marianne, and Klotz, Evelyne

Subjects
[CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry
Published
2006

50. Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors

Author

Cheng, M K, Doumad, A B, Jiang, H, Falck, J R, McGiff, J C, and Carroll, M A

Subjects
Male, Adenosine, Adenosine A2 Receptor Agonists, Receptor, Adenosine A2A, Microcirculation, Arachidonic Acids, Cytochrome P-450 CYP2J2, Glomerular Mesangium, Rats, Rats, Sprague-Dawley, Vasodilation, 8,11,14-Eicosatrienoic Acid, Renal Artery, Cytochrome P-450 Enzyme System, Papers, cardiovascular system, Oxygenases, Animals, Epoxy Compounds, lipids (amino acids, peptides, and proteins)
Abstract

Activation of rat adenosine2A receptors (A2A R) dilates preglomerular microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs). Incubation of PGMV with a selective A2A R agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 100 microM), increased isolated PGMV EET levels to 7.57+/-1.53 ng mg-1 protein from 1.06+/-0.22 ng mg-1 protein in controls (P0.05), without affecting hydroxyeicosatetraenoic acid (HETE) levels (10.8+/-0.69 vs 11.02+/-0.74 ng mg-1 protein). CGS 21680-stimulated EETs was abolished by preincubation with an A2A R antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) (100 microM). A selective epoxygenase inhibitor, methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; 12 microM) prevented CGS 21680-induced increase in EETs, indicating inhibition of de novo synthesis of EETs. In pressurized (80 mmHg) renal arcuate arteries (110-130 microm) preconstricted with phenylephrine (20 nM), superfusion with CGS 21680 (0.01-10 microM) increased the internal diameter (i.d.) concentration-dependently; vasodilation was independent of nitric oxide and cyclooxygenase activity. CGS 21680 (10 microM) increased i.d. by 32+/-6 microm; vasodilation was prevented by inhibition of EET synthesis with MS-PPOH. Addition of 3 nM 5,6-EET, 8,9-EET and 11,12-EET increased i.d. by 53+/-9, 17+/-4 and 53+/-5 microm, respectively, whereas 14,15-EET was inactive. The responses to 5,6-EET were, however, significantly inhibited by indomethacin. We conclude that 11,12-EET is the likely mediator of A2A R-induced dilation of rat PGMV. Activation of A2A R coupled to de novo EET stimulation may represent an important mechanism in regulating preglomerular microvascular tone. British Journal of Pharmacology (2004) 141, 441-448. doi:10.1038/sj.bjp.0705640

Published
2004

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