28 results on '"Caccioppoli C"'
Search Results
2. Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells
- Author
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Perrini, S., Laviola, L., Cignarelli, A., Melchiorre, M., De Stefano, F., Caccioppoli, C., Natalicchio, A., Orlando, M. R., Garruti, G., De Fazio, M., Catalano, G., Memeo, V., Giorgino, R., and Giorgino, F.
- Published
- 2008
- Full Text
- View/download PDF
3. The topographical expression map of chromosome 21 genes
- Author
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Reymond, A., Marigo, V., Yaylaoglu, M., Leoni, A., Lyle, R., Caccioppoli, C., Ucla, C., Guipponi, M., Banfi, S., Eichele, G., Antonarakis, S., and Ballabio, A.
- Subjects
Human genetics -- Research ,Down syndrome -- Genetic aspects ,Genetic disorders -- Research ,Biological sciences - Published
- 2001
4. Natural antisense transcripts associated with genes involved in eye development
- Author
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Alfano G, Vitiello C, Caccioppoli C, Caramico T, Carola A, Szego MJ, McInnes RR, Auricchio A, BANFI, Sandro, Alfano, G, Vitiello, C, Caccioppoli, C, Caramico, T, Carola, A, Szego, Mj, Mcinnes, Rr, Auricchio, A, and Banfi, Sandro
- Published
- 2005
5. Natural antisense transcripts (NATs) associated with genes involved in eye development
- Author
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ALFANO G., VITIELLO C., CACCIOPPOLI C., CARAMICO T., CAROLA A., SZEGO M. J., MCINNES R. R., BANFI S. ., AURICCHIO, ALBERTO, Alfano, G., Vitiello, C., Caccioppoli, C., Caramico, T., Carola, A., Szego, M. J., Mcinnes, R. R., Auricchio, Alberto, and Banfi, S. .
- Published
- 2005
6. Pcp4l1, a novel gene encoding a Pcp4-like polypeptide, is expressed in specific domains of the developing brain
- Author
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Bulfone A, Caccioppoli C, Pardini C, Faedo A, Martinez S, BANFI, Sandro, Bulfone, A, Caccioppoli, C, Pardini, C, Faedo, A, Martinez, S, and Banfi, Sandro
- Published
- 2004
7. Expression atlas of the mouse orthologues of the Williams-Beuren syndrome critical region genes
- Author
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Reymond, A., Yaylaoglu, M., Merla, G., Thaller, C., Caccioppoli, C., Ucla, C., Montanaro, D., Chen, T. M., Scamuffa, N., Ballabio, A., Antonarakis, S. E., Eichele, G., and Marigo, Valeria
- Subjects
malattia genetica ,cromosoma 7 ,ibridazione in situ - Published
- 2003
8. Expression Atlas of the mouse orthologues of the human chromosome 21 genes
- Author
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Reymond, A., Marigo, Valeria, Yaylaoglu, M., Leoni, A., Ucla, C., Scamuffa, N., Banfi, S., Lyle, R., Caccioppoli, C., Eichele, G., Antonarakis, S. E., and Ballabio, A.
- Subjects
ibridazione in situ ,sindrome di Down - Published
- 2002
9. Identification and characterisation of the retinitis pigmentosa 1-like1 gene (RP1L1): a novel candidate for retinal degenerations.
- Author
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Conte, I., Lestingi, M., Hollander, A.I. den, Alfano, G., Ziviello, C., Pugliese, M., Circolo, D., Caccioppoli, C., Ciccodicola, A., Banfi, S., Conte, I., Lestingi, M., Hollander, A.I. den, Alfano, G., Ziviello, C., Pugliese, M., Circolo, D., Caccioppoli, C., Ciccodicola, A., and Banfi, S.
- Abstract
Item does not contain fulltext, Retinitis pigmentosa (RP) is the most common form of inherited retinopathy, with an approximate incidence of 1 in 3700 individuals worldwide. Mutations in the retinitis pigmentosa 1 (RP1) gene are responsible for about 5-10% cases of autosomal dominant RP. The RP1 gene is specifically expressed in the photoreceptor layers of the postnatal retina and encodes a predicted protein characterised by the presence of two doublecortin (DC) domains, known to be implicated in microtubule binding. We identified and characterised, both in human and in mouse, a novel mammalian gene, termed Retinitis Pigmentosa1-like1 (RP1L1), because of its significant sequence similarity to the RP1 gene product. The sequence homology between RP1 and RP1L1 was found to be mostly restricted to the DC domains and to the N-terminal region, including the first 350 amino acids. The RP1L1 gene was also found to be conserved in distant vertebrates, since we identified a homologue in Fugu rubripes (pufferfish). Similar to RP1, RP1L1 expression is restricted to the postnatal retina, as determined by semiquantitative reverse transcriptase-PCR and Northern analysis. The retina-specific expression and the sequence similarity to RP1 render RP1L1 a potential candidate for inherited retinal disorders.
- Published
- 2003
10. Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells
- Author
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Perrini, S., primary, Laviola, L., additional, Cignarelli, A., additional, Melchiorre, M., additional, De Stefano, F., additional, Caccioppoli, C., additional, Natalicchio, A., additional, Orlando, M. R., additional, Garruti, G., additional, De Fazio, M., additional, Catalano, G., additional, Memeo, V., additional, Giorgino, R., additional, and Giorgino, F., additional
- Published
- 2007
- Full Text
- View/download PDF
11. 40 EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
- Author
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Veitenhansl, M., Stegner, K., Hierl, F-X, Dieterle, C., Feldmeier, H., Gutt, B., Landgraf, R., Garrow, A. P., Vileikyte, L., Findlow, A., Waterman, C., Boulton, A. J. M., Shankhdhar, K., Shankhdhar, L., Shankhdhar, U., Petrova, N. L., Foster, A. V. M., Edmonds, M. E., Ferraresi, R., Caravaggi, C., Giglio, R., Cavaiani, P., Pogliaghi, I., Sommariva, E., Katz, I. A., Harlan, A., Miranda-Palma, B., Prieto-Sanchez, L., Armstrong, D. G., Bowker, J. H., Mizel, M. S., Cernea, S., Wohlgelernter, J., Kidron, M., Modi, P., Raz, I., Arbit, E., Nosek, L., Kapitza, C., Beckett, P., Gelfand, R., Goldberg, M., Heise, T., Testa, M. A., Turner, R. R., Hayes, J. F., Scranton, R. E., Simonson, D. C., Yang, Y-W, Hsu, Y-J, Naujok, O., Francini, F., Jorns, A., Tiedge, M., Lenzen, S., Abdel-Wahab, Y. H. A., Marenah, L., Orr, D. F., Shaw, C., Flatt, P. R., Chokkalingam, K., Mansell, P. I., Clausen, P., Ekbom, P., Damm, P., Feldt-Rasmussen, U., Nielsen, B., Mathiesen, E. R., Feldt-Rasmussen, B., Dewan, S., Da Silva, N., Ternan, P. Mc, Leong, K. S., Wilding, J. P. H., Asatiani, N., Kurashvili, R., Dundua, M., Shelestova, E., Pagava, K., Ramazashvili, M., Hod, M., Smirnov, S., Petersen, J. L. A., Justesen, T. I., Ringholm Nielsen, L., Muller, C., Hojlund, K., Wensaas, A., Kase, E. T., Aas, V., Rustan, A. C., Thoresen, G. H., Levin, K., Beck-Nielsen, H., Gaster, M., Im, S-S, Kang, S-Y, Kim, S-Y, Ahn, Y-H, Lihn, A. S., Schmoll, D., Werner, T., Kienitz, A., Meyer, M., Barthel, A., Ailett, F., Sutherland, C., Walther, R., Grempler, R., Sasson, S., Reich, R., Tenenbaum, T., Alpert, E., Anfossi, G., Russo, I., Traversa, M., Massucco, P., Mattiello, L., Doronzo, G., Trovati, M., Lally, S., Tan, C. Y., Owens, D., Tomkin, G. H., Porchay, I., Pean, F., Bellili, N., Betoulle, D., Balkau, B., Tichet, J., Marre, M., Fumeron, F., Group D.E.S.I.R., Chatellier, G., Alhenc-Gelas, F., Diabhycar, Study Group, Nichols, G. A., Brown, J. B., Hayes, R. P., Bowman, L., Drexel, H., Saely, C. H., Marte, T., Benzer, W., Langer, P., Hoefle, G., Moll, W., Aczel, S., Karagiannis, E., Lubben, G., Urquhart, R., Edwards, G., Bruce, S., Howlett, H. S. C., Cugnardey, N., Turner, K. C., Park, J-S, Fiedorek, F. T., Avogaro, A., Gallo, A., Pinton, P., Rizzuto, R., Murphy, E., Ceolotto, G., Caterson, I., Guy-Grand, B., Hill, J., Barone, M., Aiello, A., Allochis, G., Borzi, V., Cannata, F., Caronna, S., D Avanzo, A., Elli, R., Formoso, G., Paroli, A., Scardapane, R., Sorichetti, P., Tatti, P., Viviani, G., Santeusanio, F., Italian Repaglinide Study Group, Manzella, D., Grella, R., Abbatecola, A. M., Paolisso, G., Sondergaard, L. G., Monster, T. B. M., Johnsen, S. P., Olsen, M. L., Mclaughlin, J. K., Sorensen, H. T., Lervang, H. H., Rungby, J., Lyssenko, V., Fredriksson, J., Almgren, P., Anevski, D., Orho-Melander, M., Sjogren, M., Tuomi, T., Groop, L., Jaziri, R., Aubert, R., Tuomilehto, J., Hu, G., Jousilahti, P., Peltonen, M., Lindstrom, J., Laina, A., Alevizaki, M., Philippou, G., Souvatzoglou, A., Anastasiou, E., Alba, S., Metcalf, B. S., Voss, L. D., Jeffery, A. N., Wilkin, T. J., Gluimer, C., Colagiuri, S., Vistisen, D., Borch-Johnsen, K., Haynes, A., Bower, C., Bulsara, M. K., Jones, T. W., Davis, E. A., Mortensen, H. B., Hougaard, P., Holl, R., Swift, P., Pociot, F., Knip, M., Hansen, L., Szadkowska, A., Pietrzak, I., Zmyslowska, A., Wyka, K., Bodalski, J., Holl, R. W., Swift, R., Hougaard, R., Gerstl, E-M, Engelsberger, I., Rabl, W., Rosenbauer, J., Grobe, H., Hofer, S. E., Krause, U., DPV-Wiss-Study Group, Dabelea, D., Morgan, T., Pettitt, D. J., Dolan, L., Mayer-Davis, E. J., Pihoker, C., Hillier, T. A., Imperatore, G., Ruggiero, A., Hamman, R. E., Stylianou, A., Tentolouris, N., Perrea, D., Tselepis, A. D., Lourida, E., Kitsou, E., Katsilambros, N., Vedovato, M., Dodesini, A. R., Lepore, G., Tiengo, A., Trevisan, R., Penno, G., Miccoli, R., Pucci, L., Lucchesi, D., Bandinelli, S., Fotino, C., Triscornia, S., Baldassari, E., Del Prato, S., Reboldi, P., Santeusanio, E., Fuller, J., Langham, R. G., Gow, R. M., Zhang, Y., Kelly, D. J., Christensen, P. K., Parving, H-H, Gilbert, R. E., Chibalin, A. V., Zhong, Z., Kotova, O., Davidescu, A., Ehren, I., Ekberg, K., Wahren, J., Wassef, L., Buckley, A. J., Rooney, K. B., Briody, J., Thompson, M., Ozanne, S. E., Thompson, C. H., Chamson-Reig, A., Summers, K., Arany, E. J. R., Hill, D. J., Solerte, S. B., Gazzaruso, C., Locatelli, E., Precerutti, S., Schifino, N., Ferrari, E., Fioravanti, M., Phenekos, C. V., Ginis, A., Fragaki, I., Chalkiadaki, M., Tzioras, C., Powell, L. A., Mcguire, G. M., Jewhurst, V., Trimble, E. R., Rasmussen, B. M., Vessby, B., Uusitupa, M., Berglund, L., Pedersen, E., Riccardi, G., Rivellese, A. A., Tapsell, L., Hermansen, K., Kanwu, Study Group, Da Silva Xavier, G., Rutter, J., Rutter, G. A., Briaud, I. M., Lingohr, M. K., Dickson, L. M., Mccuaig, J. R., Lawrence, J. C., Rhodes, C. J., Wikstrom, J. D., Katzman, S. M., Shirihai, O. S., Yang, J., Deng, S., Wang, X., Hessner, M. J., Wu, J., Wong, R. K., Sukumvanich, S., Markman, J. F., Naji, A., Wolf, B. A., Gao, Z., Rubi, B., Del Arco, A., Satrustegui, J., Maechler, P., Del Guerra, S., Lupi, R., Bugliani, M., Sbrana, S., Torri, S., Boggi, U., Vistoli, F., Mosca, F., Marchetti, P., Rennings, A. J. M., Smits, P., Stewart, M. W., Tack, C. J. J., Li, L., Nystrom, T., Gutniak, M., Ahren, B., Holst, J., Sjoholm, A., Gomes, M. B., Cailleaux, S., Tibirica, E., Albertini, J-P, Chen, H., Mather, R., Valensi, P. E., Chisalita, S. I., Arnqvist, H. J., Kraenkel, N., Adams, V., Linke, A., Gielen, S., Schuler, G., Humbrecht, R., Cipollone, F., Iezzi, A., Fazia, M., Pini, B., Cucurullo, C., Cesare, D., Schmidt, A. M., Mazurek, T., Zang, L. F., Mannion, J., Diehl, J., Martin, J., Martella, A., Zalewski, A., Shi, Y., Otter, W., Winter, M., Doering, W., Standi, E., Schnell, O., Kragelund, C., Kober, L., Faber, J., Hildebrandt, P., Steffensen, R., Pankowska, E., Szypowska, A., Lipka, M., Herwig, J., Scholl-Schilling, G., Bohles, H., Robertson, K. J., Schonle, E., Gucev, Z., Mordhorst, L., Tamer, S. C., Gall, M-A, Ludvigsson, J., Hoogma, R. P. L., Hammond, P. J., Gomis, R., Kerr, D., Bruttomesso, D., Bouter, P., Wiefels, K. J., La Calle, H., Schweitzer, D. H., Pfohl, M., Torlone, E., Krinelke, L. G., 205-Nations Study Group, Conget, I., Storms, F., Rodriguez, J., Leperlier, C., Davies, M., At Lantus, Study Group, Peter, R., Luzio, S. D., Dunseath, G., Miles, A., Hare, B., Backx, K., Pauvaday, V., Owens, D. R., Caselli, A., Marfia, G. A., Battista, C., Veves, A., Spallone, V., Uccioli, L., Gonzalez, J. S., Peyrot, M. F., Rubin, R. R., Leventhal, H., Scheffler, N., Ulbrecht, J. S., Cavanagh, P. R., Boulton, A. J., Perrin, N. A., Oglesby, A., Bastyr, E. J., Ziegler, D., Siekierka-Kleiser, E., Meyer, B., Schweers, M., Selvarajah, D., Wilkinson, I. D., Emery, C. J., Shaw, P. J., Griffiths, P. D., Tesfaye, S., Obrosova, I. G., Arezzo, J., Phillips, K., Fidarestat Study Group, Gribble, F. M., Williams, L., Reimann, F., Iakoubov, R., Whiteside, C., Brubaker, P. L., Acitores, A., Gonzalez, N., Sancho, V., Valverde, I., Villanueva-Penacarrillo, M. L., Martin-Duce, A., Trigo, M. V., Arnes, L., Burkart, V., Ichino, N., Ohashi, A., Klein, B. S., Paxian, S., Schmid, R., Karlsen, A. E., Heding, P. E., Frobose, H., Ronn, S. G., Kruhoffer, M., Orntoft, T. F., Nerup, J., Mandrup-Poulsen, T., Billestrup, N., Cardozo, A. K., Ortis, F., Feng, Y-M, Rasschaert, J., Eylen, F., Storling, J., Herchuelz, A., Eizirik, D. L., Wang, H., Kouri, G., Wollheim, C. B., Ribaux, P., Hammar, E., Parnaud, G., Rouiller, D., Bosco, D., Halban, P., Midthjell, K., Carlsson, S., Grill, V., Lau, C., Farch, K., Glumer, C., Tetens, I., Jorgensen, T., Tillin, T., Forouhi, N., Mckeigue, P., Chaturvedi, N., Zethelius, B., Hales, C. N., Berne, C., Coleman, R. L., Stevens, R. J., Holman, R. R., Christensen, J. O., Sandbak, A., Lauritzen, T., Irwin, N., Gault, V. A., Green, B. D., Harriott, P., O Harte, F. P. M., Bouman, S. D., Urso, B., Brand, C. L., Rolin, B., Ribel, U., Schaffer, L., Maggs, D. G., Ceriello, A., Frias, J. P., Wang, Y., Ruggles, J. A., Kolterman, O. G., Piconi, L., Weyer, C., Want, L. L., Ratner, R. E., Uwaifo, G. I., Thornberry, N. A., Eiermann, G., Kim, D., Lankas, G., Leiting, B., Li, Z., Lyons, K., Petrov, A., Sinha Roy, R., Woods, A., Woods, J., Zhang, B. B., Fisher, M., Moller, D. E., Weber, A. E., Dreyer, M., Bellin, C., Schmitz, V., Roesen, R., Nescheret, A. P., Bose, A. K., Mocanu, M. M., Carr, R. D., Yellon, D. M., Manolopoulos, K., Born, S., Wagner, A., Jeziorska, M., Ben Drief, A., Bashir, M., Tomlinson, D., Malik, R. A., Zeymer, U., Schwarzmaier-D Assie, A., Petzinna, D., Chiasson, J-L, Stratton, I. M., Af Bjorkesten, C-G, Fagerudd, J., Rosengard-Barlund, M., Forsblom, C., Pettersson-Fernholm, K., Waden, J., Saraheimo, M., Ronnback, M., Thorn, L., Groop, P-H, Mollsten, A., Svensson, M., Kockum, I., Rudberg, S., Brismar, K., Dahlquist, G., Hovind, P., Hansen, T. K., Tarnow, L., Thiel, S., Jensen, B. R., Flyvbjerg, A., Kankova, K., Hertlova, M., Krusova, D., Schwenke, S., Ott, J., Thom, S. A. M., Mistry, P., Sjolie, A., Larsen, B., Witt, N., Hughes, A. D., Samira, H. H., Lahiry, S., Howlader, S. R., Parveen, S., Azad Khan, A. K., Clarke, P. M., Gray, A., Stevens, R., Holman, R., Phillips, L., Phillips, P. J., Chittleborough, C., Baldock, K., Taylor, A., North West Adelaide Health Study Team, Davis, W. A., Davis, T. M. E., Knuiman, M. W., Hendrie, D., Worthley, D., Nicolucci, A., Pellegrini, F., Berardis, G., Franciosi, M., Belfiglio, M., Rossi, M. C. E., Sacco, M., Valentini, M., Richardson, C. C., Jones, P., Persaud, S., Hussain, K., Clark, A., Christie, M. R., Gniuli, D., Hribal, M. L., Accili, D., Khan, M., Zervou, S., Cheung, L., Abouna, S., Ifandi, V., Pelengaris, S., Luco, R. F., Ferrer, J., Ma, D., Shield, J. P. H., Dean, W., Leclerc, I., Knauf, C., Burcelin, R., Kelsey, G., Powers, A. C., Shostak, A., Ferrara, N., Poffenberger, G., Jerome, W. G., Brissova, M., Geloneze, S. R., Tambascia, M. A., Pareja, J. C., Chaim, E., Silveira, H. V., Geloneze, B., Ravikumar, B., Carey, P. E., Snaar, J. E., Dheelchand, D., Cook, D. B., Neely, D., Taylor, G., Morris, P. G., Taylor, R., Stears, A. J., Masding, M. G., Wootton, S. A., Sandeman, D. D., Klimes, I., Wein, S., Gasperikova, D., Ukropec, J., Wiernsperger, N., Sebokova, E., Manco, M., Mingrone, G., Granato, L., Greco, A. V., Nanni, G., Castagneto, M., Vidal, H., Calvani, M., Ferrannini, E., Alvarsson, M., Sundkvist, G., Lager, I., Henricsson, M., Berntorp, K., Fernqvist-Forbes, E., Steen, L., Orn, T., Shutler, S., Bianchi-Biscay, M., Rosenstock, J., Sugimoto, D., Strange, P., Stewart, J., Soltes Rak, E., Dailey, G., Kloos, C., Muller, U., Samann, A., Femerling, M., Risse, A., Jecht, M., Haak, T., Garg, R., Lawrence, I. G., Akinsola, M. O., Davies, M. J., Mcnally, P. G., Garber, A. J., Kim, H., Draeger, E., Aydin, L., Sengul, A., Kurklu, A., Ucak, S., Basat, O., Seber, S., Altuntas, Y., Jin, J., Yu, Y., Yu, H., Zhang, X., Mattoo, V., Eckland, D., Widel, M., Duran, S., Fajardo, C., Strand, J., Knight, D., Oakley, D., Tan, M., Sato, A., Nagao, M., Aki, N., Nakagami, T., Iwamoto, Y., Zhou, Z., Li, X., Huang, G., Yan, X., Yang, L., Peng, J., Wang, J., Tan, S., Tang, W., Furnsinn, C., Brunmair, B., Wagner, L., Gras, F., Artwohl, M., Zierhut, B., Waldhausl, W., Shine, B. L., Hopkins, D., Anand, V., Lim, E., Raval, U., Sharp, P., Corder, R., Lipkin, D., Lahiri, A., Bartnik, M., Ryden, L., Ferrari, R., Malmberg, K., Pyorala, K., Simoons, M. L., Standl, E., Soler-Soler, J., Ohrvik, J., Euro Heart Survey Investigators, Bruce, D. G., Starkstein, S. E., Schauer, U. J. W., Astrup, A. S., Pietraszek, L., Nielsen, F. S., Rossing, P., Ali, S., Smidt, U. M., Yokoyama, H., Pavkov, M. E., Knowler, W. C., Bennett, P. H., Nelson, R. G., Lopez-Alba, A., Morcillo, L., Caballero, A., Montoya, L., Jimenez, A., Maceira, B., Lewis, J. B., Ravid, M., Wajman, A., Tadgell, C., Remuzzi, G., Hunsicker, L. G., Wessman, M., Taskinen, M-R, FinnDiane Study Group, Pugliese, G., Amadio, L., Menini, S., Oddi, G., Ricci, C., Iacobini, C., Pricci, F., Sorcini, M., Pesce, C., Migliaccio, E., Giorgio, M., Pelicci, P., Di Mario, U., Lassila, M., Jandeleit-Dahm, K., Seah, K. K., Calkin, A. C., Allen, T. J., Cooper, M. E., Lopes Faria, J. M., Cavakcanti, T. C., Silva, K. C., Ferrari, A. L., Lopes Faria, J. B., Cellek, S., Foxwell, N. A., Cotter, M. A., Cameron, N. E., Tennagels, N., Jordan, H., Stahl, P., Voss, M. D., Welte, S., Werner, U., Lehmann, R., Moeschel, K., Baumgartner, F., Oeckinghaus, A., Beck, A., Weigert, C., Hennige, A., Schleicher, E. D., Haring, H. U., Mussig, K., Staiger, H., Haring, H-U, Natalicchio, A., Laviola, L., Tullio, C., Renna, L., Giorgino, R., Giorgino, F., Falasca, M., Maffucci, T., Park, D., Kang, S., Song, J., Lee, D., Lee, Y., Hariharan, N., Kunselman, L., Gu, L., Sasseville, V., Harrity, T., Cheng, P. T. W., Pratley, R. E., Schweizer, A., Mills, D., Kim, T-H, Song, X-L, Poelje, P. D., Potter, S. C., Dang, Q., Fujitaki, J. M., Linemeyer, D. L., Landau, B. R., Erion, M. D., Pankop, M., Golay, A., Despres, J., Sjostrom, L., Lawlor, D. L., Legg, K. T., Ur, E., Houweling, S. T., Kleefstra, N., Meyboom-De Jong, B., Bilo, H. J. G., Schlomer, G. J., Meyer, G., Kasper, J., Muhlhauser, I., Young, B., Taylor, J., Friede, T., Hollis, S., Mason, J., Long, A., Gambling, T., Pauline, L., Burns, E., New, J., Gibson, M., Betteridge, D. J., Leiter, L. A., Audit, Investigators, Whitty, P. M., Eccles, M. P., Hawthorne, G., Grimshaw, J., Steen, I. N., Vanoli, A., Wood, L., Speed, C., Mcdowell, D., Rewers, M., Maahs, D., Wadwa, R., Eckel, R., Tracy, R., Pfutzner, A., Strotmann, H-J, Schulze, J., Hohberg, C., Pahler, S., Forst, T., Ambery, P. D., Sydall, H., Cooper, C., Dennison, E., Sayer, A. Aihie, Barker, D., Phillips, D., Lalic, N. M., Ostojic, M., Lalic, K., Zamaklar, M., Jotic, A., Ilic, M., Rajkovic, N., Lukic, L., Milicic, T., Verges, B., Zeller, M., Steg, P. G., Beer, J. C., Brisard, C., Brindisi, M. C., Dentan, G., Laurent, Y., Janin-Manificat, L., Makki, H., Ravisy, J., Cottin, Y., Ajjan, R. A., Grant, P. J., Futers, T. S., Brown, J. M., Carter, A. M., Rasmussen, M. S., Bruun, J. M., Pedersen, S. 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12. Identification and characterisation of the retinitis pigmentosa 1-like1 gene (RP1L1): a novel candidate for retinal degenerations
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Sandro Banfi, Giovanna Alfano, Marta Lestingi, Diego Circolo, Alfredo Ciccodicola, Ivan Conte, Carmela Ziviello, Anneke I. den Hollander, Cristina Caccioppoli, Mariarosaria Pugliese, Conte, I., Lestingi, M., den Hollander, A., Alfano, G., Ziviello, C., Pugliese, M., Circolo, D., Caccioppoli, C., Ciccodicola, A., Banfi, S., Conte, I, Lestingi, M, den Hollander, A, Alfano, G, Ziviello, C, Pugliese, M, Circolo, D, Caccioppoli, C, Ciccodicola, A, and Banfi, Sandro
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Sequence analysis ,Amino Acid Motifs ,Molecular Sequence Data ,Retinitis ,Biology ,Retina ,Homology (biology) ,Gene product ,Mice ,Sequence Analysis, Protein ,DC domain ,Retinitis pigmentosa ,Genetics ,medicine ,Animals ,Neurosensory disorders [UMCN 3.3] ,Amino Acid Sequence ,Eye Proteins ,Gene ,Genetics (clinical) ,Animal ,Gene Expression Profiling ,Retinal Degeneration ,Eye Protein ,Human diseases ,medicine.disease ,Molecular biology ,RP1 ,eye diseases ,Takifugu ,Doublecortin ,Gene expression profiling ,Gene identification ,Genetic defects of metabolism [UMCN 5.1] ,Organ Specificity ,Amino Acid Motif ,biology.protein ,RP1L1 ,sense organs - Abstract
Item does not contain fulltext Retinitis pigmentosa (RP) is the most common form of inherited retinopathy, with an approximate incidence of 1 in 3700 individuals worldwide. Mutations in the retinitis pigmentosa 1 (RP1) gene are responsible for about 5-10% cases of autosomal dominant RP. The RP1 gene is specifically expressed in the photoreceptor layers of the postnatal retina and encodes a predicted protein characterised by the presence of two doublecortin (DC) domains, known to be implicated in microtubule binding. We identified and characterised, both in human and in mouse, a novel mammalian gene, termed Retinitis Pigmentosa1-like1 (RP1L1), because of its significant sequence similarity to the RP1 gene product. The sequence homology between RP1 and RP1L1 was found to be mostly restricted to the DC domains and to the N-terminal region, including the first 350 amino acids. The RP1L1 gene was also found to be conserved in distant vertebrates, since we identified a homologue in Fugu rubripes (pufferfish). Similar to RP1, RP1L1 expression is restricted to the postnatal retina, as determined by semiquantitative reverse transcriptase-PCR and Northern analysis. The retina-specific expression and the sequence similarity to RP1 render RP1L1 a potential candidate for inherited retinal disorders.
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- 2003
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13. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. 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Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
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0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
14. Human chromosome 21 gene expression atlas in the mouse
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Valeria Marigo, Emmanouil T. Dermitzakis, Antonio Leoni, Catherine Ucla, Nathalie Scamuffa, Stylianos E. Antonarakis, Andrea Ballabio, Murat B. Yaylaoglu, Sandro Banfi, Gregor Eichele, Alexandre Reymond, Cristina Caccioppoli, Robert Lyle, Reymond, A, Marigo, V, Yaylaoglu, Mb, Leoni, A, Ucla, C, Scamuffa, N, Caccioppoli, C, Dermitzakis, Et, Lyle, R, Banfi, S, Eichele, G, Antonarakis, Se, Ballabio, Andrea, Banfi, Sandro, and Ballabio, A.
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TBX1 ,cromosoma 21 ,sindrome di Down ,mRNA ,espressione in situ ,Embryo, Mammalian/embryology/metabolism ,RNA, Messenger/genetics/metabolism ,In situ hybridization ,ibridazione in situ ,Biology ,Sequence Homology, Nucleic Acid ,Gene expression ,medicine ,Animals ,Humans ,Gene ,In Situ Hybridization ,Transcription, Genetic/genetics ,Genetics ,ddc:616 ,Multidisciplinary ,Mice/ embryology/ genetics ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Gene Expression Regulation, Developmental ,Genomics ,medicine.disease ,Chromosomes, Human, Pair 21/ genetics ,Down Syndrome/genetics/pathology/physiopathology ,Human genome ,Trisomy ,Chromosome 21 ,Functional genomics - Abstract
Genome-wide expression analyses have a crucial role in functional genomics. High resolution methods, such as RNA in situ hybridization provide an accurate description of the spatiotemporal distribution of transcripts as well as a three-dimensional 'in vivo' gene expression overview(1-5). We set out to analyse systematically the expression patterns of genes from an entire chromosome. We chose human chromosome 21 because of the medical relevance of trisomy 21 (Down's syndrome)(6). Here we show the expression analysis of all identifiable murine orthologues of human chromosome 21 genes (161 out of 178 confirmed human genes) by RNA in situ hybridization on whole mounts and tissue sections, and by polymerase chain reaction with reverse transcription on adult tissues. We observed patterned expression in several tissues including those affected in trisomy 21 phenotypes (that is, central nervous system, heart, gastrointestinal tract, and limbs). Furthermore, statistical analysis suggests the presence of some regions of the chromosome with genes showing either lack of expression or, to a lesser extent, co-expression in either lack of expression or, to a lesser extent, co-expression in specific tissues. This high resolution expression 'atlas' of an entire human chromosome is an important step towards the understanding of gene function and of the pathogenetic mechanisms in Down's syndrome.
- Published
- 2002
15. The p66 Shc Redox Protein and the Emerging Complications of Diabetes.
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Biondi G, Marrano N, Borrelli A, Rella M, D'Oria R, Genchi VA, Caccioppoli C, Cignarelli A, Perrini S, Laviola L, Giorgino F, and Natalicchio A
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- Humans, Apoptosis, Cellular Senescence, Oxidation-Reduction, Diabetic Nephropathies, Peripheral Arterial Disease, Diabetes Mellitus
- Abstract
Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66
Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.- Published
- 2023
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16. Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System.
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D'Oria R, Genchi VA, Caccioppoli C, Calderoni I, Marrano N, Biondi G, Borrelli A, Di Gioia L, Giorgino F, and Laviola L
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- Humans, Obesity complications, Pericardium, Liver, Adipose Tissue, Cardiovascular Diseases complications
- Abstract
Obesity with its associated complications represents a social, economic and health problem of utmost importance worldwide. Specifically, obese patients carry a significantly higher risk of developing cardiovascular disease compared to nonobese individuals. Multiple molecular mechanisms contribute to the impaired biological activity of the distinct adipose tissue depots in obesity, including secretion of proinflammatory mediators and reactive oxygen species, ultimately leading to an unfavorable impact on the cardiovascular system. This review summarizes data relating to the contribution of the main adipose tissue depots, including both remote (i.e., intra-abdominal, hepatic, skeletal, pancreatic, renal, and mesenteric adipose fat), and cardiac (i.e., the epicardial fat) adipose locations, on the cardiovascular system. Finally, we discuss both pharmacological and non-pharmacological strategies aimed at reducing cardiovascular risk through acting on adipose tissues, with particular attention to the epicardial fat.
- Published
- 2022
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17. The p66Shc Protein Mediates Insulin Resistance and Secretory Dysfunction in Pancreatic β-Cells Under Lipotoxic Conditions.
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Biondi G, Marrano N, Dipaola L, Borrelli A, Rella M, D'Oria R, Genchi VA, Caccioppoli C, Porreca I, Cignarelli A, Perrini S, Marchetti P, Vincenti L, Laviola L, Giorgino F, and Natalicchio A
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- Animals, Apoptosis, C-Peptide metabolism, Humans, Insulin metabolism, Mice, Palmitates metabolism, Palmitates pharmacology, Signal Transduction, Src Homology 2 Domain-Containing, Transforming Protein 1 genetics, Insulin Resistance, Insulin-Secreting Cells metabolism, Src Homology 2 Domain-Containing, Transforming Protein 1 metabolism
- Abstract
We evaluated the role of the p66Shc redox adaptor protein in pancreatic β-cell insulin resistance that develops under lipotoxic conditions and with excess body fat. Prolonged exposure to palmitate in vitro or the presence of overweight/obesity augmented p66Shc expression levels and caused an impaired ability of exogenous insulin to increase cellular insulin content and secreted C-peptide levels in INS-1E cells and human and murine islets. In INS-1E cells, p66Shc knockdown resulted in enhanced insulin-induced augmentation of insulin content and C-peptide secretion and prevented the ability of palmitate to impair these effects of insulin. Conversely, p66Shc overexpression impaired insulin-induced augmentation of insulin content and C-peptide secretion in both the absence and presence of palmitate. Under lipotoxic condition, the effects of p66Shc are mediated by a p53-induced increase in p66Shc protein levels and JNK-induced p66Shc phosphorylation at Ser36 and appear to involve the phosphorylation of the ribosomal protein S6 kinase at Thr389 and of insulin receptor substrate 1 at Ser307, resulting in the inhibition of insulin-stimulated protein kinase B phosphorylation at Ser473. Thus, the p66Shc protein mediates the impaired β-cell function and insulin resistance induced by saturated fatty acids and excess body fat., (© 2022 by the American Diabetes Association.)
- Published
- 2022
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18. Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism.
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Genchi VA, Rossi E, Lauriola C, D'Oria R, Palma G, Borrelli A, Caccioppoli C, Giorgino F, and Cignarelli A
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- Adipose Tissue, Humans, Male, Obesity drug therapy, Testis, Testosterone therapeutic use, Hypogonadism complications, Hypogonadism drug therapy, Insulin Resistance
- Abstract
Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic-pituitary-gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus-pituitary-testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.
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- 2022
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19. Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity.
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Palma G, Sorice GP, Genchi VA, Giordano F, Caccioppoli C, D'Oria R, Marrano N, Biondi G, Giorgino F, and Perrini S
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- Adipokines metabolism, Humans, Inflammasomes metabolism, Inflammation metabolism, Adipose Tissue metabolism, Obesity, Morbid metabolism
- Abstract
Obesity is a chronic disease caused by an excess of adipose tissue that may impair health by altering the functionality of various organs, including the lungs. Excessive deposition of fat in the abdominal area can lead to abnormal positioning of the diaphragm and consequent reduction in lung volume, leading to a heightened demand for ventilation and increased exposure to respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and obstructive sleep apnoea. In addition to mechanical ventilatory constraints, excess fat and ectopic deposition in visceral depots can lead to adipose tissue dysfunction, which promotes metabolic disorders. An altered adipokine-secretion profile from dysfunctional adipose tissue in morbid obesity fosters systemic, low-grade inflammation, impairing pulmonary immune response and promoting airway hyperresponsiveness. A potential target of these adipokines could be the NLRP3 inflammasome, a critical component of the innate immune system, the harmful pro-inflammatory effect of which affects both adipose and lung tissue in obesity. In this review, we will investigate the crosstalk between adipose tissue and the lung in obesity, highlighting the main inflammatory mediators and novel therapeutic targets in preventing pulmonary dysfunction.
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- 2022
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20. Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?
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Genchi VA, D'Oria R, Palma G, Caccioppoli C, Cignarelli A, Natalicchio A, Laviola L, Giorgino F, and Perrini S
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- Animals, Biomarkers, Body Temperature Regulation, Disease Management, Disease Susceptibility, Energy Metabolism, Humans, Hypothalamus metabolism, Leptin blood, Leptin deficiency, Obesity diagnosis, Obesity etiology, Obesity therapy, Thermogenesis, Treatment Outcome, Leptin metabolism, Obesity metabolism, Signal Transduction
- Abstract
Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.
- Published
- 2021
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21. Reduced SIRT1 and SIRT2 expression promotes adipogenesis of human visceral adipose stem cells and associates with accumulation of visceral fat in human obesity.
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Perrini S, Porro S, Nigro P, Cignarelli A, Caccioppoli C, Genchi VA, Martines G, De Fazio M, Capuano P, Natalicchio A, Laviola L, and Giorgino F
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- Adipocytes metabolism, Adult, Cells, Cultured, Female, Gene Knockdown Techniques, Humans, Male, Middle Aged, Sirtuin 1 analysis, Sirtuin 1 genetics, Sirtuin 2 analysis, Sirtuin 2 genetics, Stem Cells metabolism, Adipogenesis physiology, Intra-Abdominal Fat cytology, Intra-Abdominal Fat metabolism, Obesity metabolism, Sirtuin 1 metabolism, Sirtuin 2 metabolism
- Abstract
Background/objectives: The histone deacetylases SIRT1 and SIRT2 have been shown to be involved in the differentiation of rodent adipocyte precursors. In light of the differences in gene expression and metabolic function of visceral (V) and subcutaneous (S) adipose tissue (AT) and their resident cells, the aim of this study was to investigate the role of SIRT1 and SIRT2 in the differentiation of adipose stem cells (ASCs) isolated from SAT and VAT biopsies of nondiabetic obese and nonobese individuals., Methods: Human ASCs were isolated from paired SAT and VAT biopsies obtained from 83 nonobese and 92 obese subjects and were differentiated in vitro. Adipogenesis was evaluated by analyzing the lipid deposition using an image processing software, and gene expression by RT-qPCR. SIRT1 and SIRT2 protein expression was modified by using recombinant adenoviral vectors., Results: Visceral but not subcutaneous ASCs from obese subjects showed an intrinsic increase in both adipogenesis and lipid accumulation when compared with ASCs from nonobese subjects, and this was associated with reduced SIRT1 and SIRT2 mRNA and protein levels. Moreover, adipose tissue mRNA levels of SIRT1 and SIRT2 showed an inverse correlation with BMI in the visceral but not subcutaneous depot. Overexpression of SIRT1 or SIRT2 in visceral ASCs from obese subjects resulted in inhibition of adipocyte differentiation, whereas knockdown of SIRT1 or SIRT2 in visceral ASCs from nonobese subjects enhanced this process. Changes in SIRT1 or SIRT2 expression and adipocyte differentiation were paralleled by corresponding changes in PPARG, CEBPA, and other genes marking terminal adipocyte differentiation., Conclusions: SIRT1 and SIRT2 modulate the differentiation of human ASC. Reduced expression of SIRT1 and SIRT2 may enhance the differentiation capacity of visceral ASC in human obesity, fostering visceral adipose tissue expansion.
- Published
- 2020
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22. GLP-1 Receptor Activation Inhibits Palmitate-Induced Apoptosis via Ceramide in Human Cardiac Progenitor Cells.
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Leonardini A, D'Oria R, Incalza MA, Caccioppoli C, Andrulli Buccheri V, Cignarelli A, Paparella D, Margari V, Natalicchio A, Perrini S, Giorgino F, and Laviola L
- Subjects
- Cells, Cultured, Exenatide, Glucagon-Like Peptide 1 analogs & derivatives, Humans, Myocytes, Cardiac metabolism, Signal Transduction drug effects, Spheroids, Cellular drug effects, Spheroids, Cellular metabolism, Stem Cells metabolism, Apoptosis drug effects, Ceramides metabolism, Glucagon-Like Peptide-1 Receptor agonists, Myocytes, Cardiac drug effects, Palmitic Acid pharmacology, Peptides pharmacology, Stem Cells drug effects, Venoms pharmacology
- Abstract
Context: Increased apoptosis of cardiomyocytes and cardiac progenitor cells (CPCs) in response to saturated fatty acids (SFAs) can lead to myocardial damage and dysfunction. Ceramides mediate lipotoxicity-induced apoptosis. Glucagonlike peptide-1 receptor (GLP1R) agonists exert beneficial effects on cardiac cells in experimental models., Objective: To investigate the protective effects of GLP1R activation on SFA-mediated apoptotic death of human CPCs., Design: Human CPCs were isolated from cardiac appendages of nondiabetic donors and then exposed to palmitate with or without pretreatment with the GLP1R agonist exendin-4. Ceramide accumulation was evaluated by immunofluorescence. Expression of key enzymes in de novo ceramide biosynthesis was studied by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Apoptosis was evaluated by measuring release of oligonucleosomes, caspase-3 cleavage, caspase activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling., Results: Exposure of the CPCs to palmitate resulted in 2.3- and 1.9-fold higher expression of ceramide synthase 5 (CERS5) and ceramide desaturase-1, respectively (P < 0.05). This was associated with intracellular accumulation of ceramide and activation of c-Jun NH2-terminal protein kinase (JNK) signaling and apoptosis (P < 0.05). Both coincubation with fumonisin B1, a specific ceramide synthase inhibitor, and CERS5 knockdown prevented ceramide accumulation, JNK activation, and apoptosis in response to palmitate (P < 0.05). Exendin-4 also prevented the activation of the ceramide biosynthesis and JNK in response to palmitate, inhibiting apoptosis (P < 0.05)., Conclusions: Excess palmitate results in activation of ceramide biosynthesis, JNK signaling, and apoptosis in human CPCs. GLP1R activation counteracts this lipotoxic damage via inhibition of ceramide generation, and this may represent a cardioprotective mechanism., (Copyright © 2017 Endocrine Society)
- Published
- 2017
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23. The p66Shc protein controls redox signaling and oxidation-dependent DNA damage in human liver cells.
- Author
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Perrini S, Tortosa F, Natalicchio A, Pacelli C, Cignarelli A, Palmieri VO, Caccioppoli C, De Stefano F, Porro S, Leonardini A, Ficarella R, De Fazio M, Cocco T, Puglisi F, Laviola L, Palasciano G, and Giorgino F
- Subjects
- Cell Culture Techniques, Forkhead Box Protein O3, Forkhead Transcription Factors metabolism, Humans, Oncogene Protein v-akt metabolism, Phosphorylation, Reactive Oxygen Species metabolism, Signal Transduction, Src Homology 2 Domain-Containing, Transforming Protein 1, DNA Damage, Fatty Liver, Alcoholic metabolism, Hepatocytes metabolism, Oxidation-Reduction, Oxidative Stress, Shc Signaling Adaptor Proteins genetics, Shc Signaling Adaptor Proteins metabolism
- Abstract
The p66Shc protein mediates oxidative stress-related injury in multiple tissues. Steatohepatitis is characterized by enhanced oxidative stress-mediated cell damage. The role of p66Shc in redox signaling was investigated in human liver cells and alcoholic steatohepatitis. HepG2 cells with overexpression of wild-type or mutant p66Shc, with Ser36 replacement by Ala, were obtained through infection with recombinant adenoviruses. Reactive oxygen species and oxidation-dependent DNA damage were assessed by measuring dihydroethidium oxidation and 8-hydroxy-2'-deoxyguanosine accumulation into DNA, respectively. mRNA and protein levels of signaling intermediates were evaluated in HepG2 cells and liver biopsies from control and alcoholic steatohepatitis subjects. Exposure to H2O2 increased reactive oxygen species and phosphorylation of p66Shc on Ser36 in HepG2 cells. Overexpression of p66Shc promoted reactive oxygen species synthesis and oxidation-dependent DNA damage, which were further enhanced by H2O2. p66Shc activation also resulted in increased Erk-1/2, Akt, and FoxO3a phosphorylation. Blocking of Erk-1/2 activation inhibited p66Shc phosphorylation on Ser36. Increased p66Shc expression was associated with reduced mRNA levels of antioxidant molecules, such as NF-E2-related factor 2 and its target genes. In contrast, overexpression of the phosphorylation defective p66Shc Ala36 mutant inhibited p66Shc signaling, enhanced antioxidant genes, and suppressed reactive oxygen species and oxidation-dependent DNA damage. Increased p66Shc protein levels and Akt phosphorylation were observed in liver biopsies from alcoholic steatohepatitis compared with control subjects. In human alcoholic steatohepatitis, increased hepatocyte p66Shc protein levels may enhance susceptibility to DNA damage by oxidative stress by promoting reactive oxygen species synthesis and repressing antioxidant pathways., (Copyright © 2015 the American Physiological Society.)
- Published
- 2015
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24. TNFα signals via p66(Shc) to induce E-Selectin, promote leukocyte transmigration and enhance permeability in human endothelial cells.
- Author
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Laviola L, Orlando MR, Incalza MA, Caccioppoli C, Melchiorre M, Leonardini A, Cignarelli A, Tortosa F, Labarbuta R, Martemucci S, Pacelli C, Cocco T, Perrini S, Natalicchio A, and Giorgino F
- Subjects
- Cell Membrane Permeability, Cells, Cultured, Coculture Techniques, E-Selectin metabolism, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Gene Expression Regulation, HL-60 Cells, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells metabolism, Humans, Mitogen-Activated Protein Kinase 8 genetics, Mitogen-Activated Protein Kinase 8 metabolism, Mitogen-Activated Protein Kinase 9 genetics, Mitogen-Activated Protein Kinase 9 metabolism, Mutation, Phosphorylation, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Reactive Oxygen Species metabolism, Shc Signaling Adaptor Proteins antagonists & inhibitors, Shc Signaling Adaptor Proteins metabolism, Signal Transduction, Src Homology 2 Domain-Containing, Transforming Protein 1, Tumor Necrosis Factor-alpha pharmacology, E-Selectin genetics, Endothelium, Vascular drug effects, Human Umbilical Vein Endothelial Cells drug effects, Shc Signaling Adaptor Proteins genetics, Transendothelial and Transepithelial Migration genetics, Tumor Necrosis Factor-alpha metabolism
- Abstract
Endothelial cells participate in inflammatory events leading to atherogenesis by regulating endothelial cell permeability via the expression of VE-Cadherin and β-catenin and leukocyte recruitment via the expression of E-Selectins and other adhesion molecules. The protein p66(Shc) acts as a sensor/inducer of oxidative stress and may promote vascular dysfunction. The objective of this study was to investigate the role of p66(Shc) in tumor necrosis factor TNFα-induced E-Selectin expression and function in human umbilical vein endothelial cells (HUVEC). Exposure of HUVEC to 50 ng/ml TNFα resulted in increased leukocyte transmigration through the endothelial monolayer and E-Selectin expression, in association with augmented phosphorylation of both p66(Shc) on Ser(36) and the stress kinase c-Jun NH2-terminal protein kinase (JNK)-1/2, and higher intracellular reactive oxygen species (ROS) levels. Overexpression of p66(Shc) in HUVEC resulted in enhanced p66(Shc) phosphorylation on Ser(36), increased ROS and E-Selectin levels, and amplified endothelial cell permeability and leukocyte transmigration through the HUVEC monolayer. Conversely, overexpression of a phosphorylation-defective p66(Shc) protein, in which Ser(36) was replaced by Ala, did not augment ROS and E-Selectin levels, nor modify cell permeability or leukocyte transmigration beyond those found in wild-type cells. Moreover, siRNA-mediated silencing of p66(Shc) resulted in marked reduction of E-Selectin expression and leukocyte transmigration. In conclusion, p66(Shc) acts as a novel intermediate in the TNFα pathway mediating endothelial dysfunction, and its action requires JNK-dependent phosphorylation of p66(Shc) on Ser(36).
- Published
- 2013
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25. Involvement of the p66Shc protein in glucose transport regulation in skeletal muscle myoblasts.
- Author
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Natalicchio A, De Stefano F, Perrini S, Laviola L, Cignarelli A, Caccioppoli C, Quagliara A, Melchiorre M, Leonardini A, Conserva A, and Giorgino F
- Subjects
- Actin Cytoskeleton metabolism, Actin Cytoskeleton physiology, Animals, Biological Transport drug effects, Biological Transport genetics, Cells, Cultured, Gene Knockdown Techniques, Glucose Transporter Type 1 metabolism, Glucose Transporter Type 1 physiology, Glucose Transporter Type 3 metabolism, Glucose Transporter Type 3 physiology, MAP Kinase Signaling System drug effects, MAP Kinase Signaling System physiology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Myoblasts, Skeletal drug effects, RNA, Small Interfering pharmacology, Rats, Shc Signaling Adaptor Proteins antagonists & inhibitors, Shc Signaling Adaptor Proteins genetics, Src Homology 2 Domain-Containing, Transforming Protein 1, Glucose metabolism, Myoblasts, Skeletal metabolism, Shc Signaling Adaptor Proteins physiology
- Abstract
The p66(Shc) protein isoform regulates MAP kinase activity and the actin cytoskeleton turnover, which are both required for normal glucose transport responses. To investigate the role of p66(Shc) in glucose transport regulation in skeletal muscle cells, L6 myoblasts with antisense-mediated reduction (L6/p66(Shc)as) or adenovirus-mediated overexpression (L6/p66(Shc)adv) of the p66(Shc) protein were examined. L6/(Shc)as myoblasts showed constitutive activation of ERK-1/2 and disruption of the actin network, associated with an 11-fold increase in basal glucose transport. GLUT1 and GLUT3 transporter proteins were sevenfold and fourfold more abundant, respectively, and were localized throughout the cytoplasm. Conversely, in L6 myoblasts overexpressing p66(Shc), basal glucose uptake rates were reduced by 30% in parallel with a approximately 50% reduction in total GLUT1 and GLUT3 transporter levels. Inhibition of the increased ERK-1/2 activity with PD98059 in L6/(Shc)as cells had a minimal effect on increased GLUT1 and GLUT3 protein levels, but restored the actin cytoskeleton, and reduced the abnormally high basal glucose uptake by 70%. In conclusion, p66(Shc) appears to regulate the glucose transport system in skeletal muscle myoblasts by controlling, via MAP kinase, the integrity of the actin cytoskeleton and by modulating cellular expression of GLUT1 and GLUT3 transporter proteins via ERK-independent pathways.
- Published
- 2009
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26. Abnormalities of insulin-like growth factor-I signaling and impaired cell proliferation in osteoblasts from subjects with osteoporosis.
- Author
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Perrini S, Natalicchio A, Laviola L, Cignarelli A, Melchiorre M, De Stefano F, Caccioppoli C, Leonardini A, Martemucci S, Belsanti G, Miccoli S, Ciampolillo A, Corrado A, Cantatore FP, Giorgino R, and Giorgino F
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Adult, Aged, Case-Control Studies, Cells, Cultured, Female, Glycogen Synthase Kinase 3 metabolism, Humans, Insulin Receptor Substrate Proteins, Intracellular Signaling Peptides and Proteins metabolism, Male, Middle Aged, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Osteoblasts drug effects, Osteoblasts metabolism, Osteoporosis metabolism, Phosphoproteins metabolism, Proto-Oncogene Proteins c-akt metabolism, Receptor, IGF Type 1 metabolism, Cell Proliferation drug effects, Insulin-Like Growth Factor I physiology, Osteoblasts pathology, Osteoporosis physiopathology, Signal Transduction physiology
- Abstract
IGF-I regulates bone acquisition and maintenance, even though the cellular targets and signaling pathways responsible for its action in human bone cells are poorly understood. Whether abnormalities in IGF-I action and signaling occur in human osteoblasts under conditions of net bone loss has not been determined. Herein we carried out a comparative analysis of IGF-I signaling in primary cultures of human osteoblasts from osteoporotic and control donors. In comparison with control cells, osteoporotic osteoblasts showed increased tyrosine phosphorylation of the IGF-I receptor in the basal state and blunted stimulation of receptor phosphorylation by IGF-I. Augmentation of basal IGF-I receptor phosphorylation was associated with coordinate increases in basal tyrosine phosphorylation of insulin receptor substrate (IRS)-2 and activation of Erk, which were also minimally responsive to IGF-I stimulation. By contrast, phosphorylation levels of IRS-1, Akt, and glycogen synthase kinase-3 were similar in the basal state in control and osteoporotic osteoblasts and showed marked increases after IGF-I stimulation in both cell populations, even though these responses were significantly lower in the osteoporotic osteoblasts. The IGF-I signaling abnormalities in osteoporotic osteoblasts were associated with reduced DNA synthesis both under basal conditions and after stimulation with IGF-I. Interestingly, treatment of the osteoporotic osteoblasts with the MAPK kinase inhibitor PD098059 reduced the elevated levels of Erk phosphorylation and increased basal DNA synthesis. Collectively, our data show that altered osteoblast proliferation in human osteoporosis may result from dysregulation of IGF-I receptor signaling, including constitutive activation of the IRS-2/Erk signaling pathway, which becomes unresponsive to IGF-I, and defective induction of the IRS-1/Akt signaling pathway.
- Published
- 2008
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27. Identification and characterisation of the retinitis pigmentosa 1-like1 gene (RP1L1): a novel candidate for retinal degenerations.
- Author
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Conte I, Lestingi M, den Hollander A, Alfano G, Ziviello C, Pugliese M, Circolo D, Caccioppoli C, Ciccodicola A, and Banfi S
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Animals, Eye Proteins metabolism, Gene Expression Profiling, Mice, Molecular Sequence Data, Organ Specificity, Retinal Degeneration metabolism, Sequence Analysis, Protein, Takifugu genetics, Eye Proteins genetics, Retina metabolism, Retinal Degeneration genetics
- Abstract
Retinitis pigmentosa (RP) is the most common form of inherited retinopathy, with an approximate incidence of 1 in 3700 individuals worldwide. Mutations in the retinitis pigmentosa 1 (RP1) gene are responsible for about 5-10% cases of autosomal dominant RP. The RP1 gene is specifically expressed in the photoreceptor layers of the postnatal retina and encodes a predicted protein characterised by the presence of two doublecortin (DC) domains, known to be implicated in microtubule binding. We identified and characterised, both in human and in mouse, a novel mammalian gene, termed Retinitis Pigmentosa1-like1 (RP1L1), because of its significant sequence similarity to the RP1 gene product. The sequence homology between RP1 and RP1L1 was found to be mostly restricted to the DC domains and to the N-terminal region, including the first 350 amino acids. The RP1L1 gene was also found to be conserved in distant vertebrates, since we identified a homologue in Fugu rubripes (pufferfish). Similar to RP1, RP1L1 expression is restricted to the postnatal retina, as determined by semiquantitative reverse transcriptase-PCR and Northern analysis. The retina-specific expression and the sequence similarity to RP1 render RP1L1 a potential candidate for inherited retinal disorders.
- Published
- 2003
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28. Human chromosome 21 gene expression atlas in the mouse.
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Reymond A, Marigo V, Yaylaoglu MB, Leoni A, Ucla C, Scamuffa N, Caccioppoli C, Dermitzakis ET, Lyle R, Banfi S, Eichele G, Antonarakis SE, and Ballabio A
- Subjects
- Animals, Down Syndrome genetics, Down Syndrome pathology, Down Syndrome physiopathology, Embryo, Mammalian embryology, Embryo, Mammalian metabolism, Genomics, Humans, In Situ Hybridization, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic genetics, Chromosomes, Human, Pair 21 genetics, Gene Expression Profiling, Gene Expression Regulation, Developmental, Mice embryology, Mice genetics, Sequence Homology, Nucleic Acid
- Abstract
Genome-wide expression analyses have a crucial role in functional genomics. High resolution methods, such as RNA in situ hybridization provide an accurate description of the spatiotemporal distribution of transcripts as well as a three-dimensional 'in vivo' gene expression overview. We set out to analyse systematically the expression patterns of genes from an entire chromosome. We chose human chromosome 21 because of the medical relevance of trisomy 21 (Down's syndrome). Here we show the expression analysis of all identifiable murine orthologues of human chromosome 21 genes (161 out of 178 confirmed human genes) by RNA in situ hybridization on whole mounts and tissue sections, and by polymerase chain reaction with reverse transcription on adult tissues. We observed patterned expression in several tissues including those affected in trisomy 21 phenotypes (that is, central nervous system, heart, gastrointestinal tract, and limbs). Furthermore, statistical analysis suggests the presence of some regions of the chromosome with genes showing either lack of expression or, to a lesser extent, co-expression in specific tissues. This high resolution expression 'atlas' of an entire human chromosome is an important step towards the understanding of gene function and of the pathogenetic mechanisms in Down's syndrome.
- Published
- 2002
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