[en] Steatosis encompasses the accumulation of droplets of fats into hepatocytes. In this work, we performed a comparative analysis of mitochondrial protein patterns found in wild-type and steatosis-affected liver using the novel technique two-dimensional differential in-gel electrophoresis (2D-DIGE). A total of 56 proteins exhibiting significant difference in their abundances were unambiguously identified. Interestingly, major proteins that regulate generation and consumption of the acetyl-CoA pool were dramatically changed during steatosis. Many proteins involved in the response to oxidative stress were also affected.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Douette, Pierre ; Université de Liège - ULiège > Bioénergétique et physiologie cellulaire
Gerkens, Pascal; Université de Liège - ULiège > Bioénergétique et physiologie cellulaire
De Pauw, Edwin ; Université de Liège - ULiège > Chimie physique, spectrométrie de masse
Leprince, Pierre ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Sluse-Goffart, Claudine; Université de Liège - ULiège > Bioénergétique et physiologie cellulaire
Sluse, Francis ; Université de Liège - ULiège > Département des sciences de la vie > Bioénergétique et physiologie cellulaire
Language :
English
Title :
Steatosis-induced proteomic changes in liver mitochondria evidenced by two-dimensional differential in-gel electrophoresis
Publication date :
2005
Journal title :
Journal of Proteome Research
ISSN :
1535-3893
eISSN :
1535-3907
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Volume :
4
Issue :
6
Pages :
2024-2031
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE] FSE - Fonds Social Européen [BE] SPW DGO6 - Service Public de Wallonie. Economie, Emploi, Recherche [BE] FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
Ravussin, A.; Bouchard, C. Human genomics and obesity: finding appropriate drug targets. Eur. J. Pharmacol. 2000, 410, 131-145.
Kopelman, P. G. Obesity as a medical problem. Nature 2000, 404, 635-643.
Pessayre, D.; Fromenty, B. NASH: a mitochondrial disease. J. Hepathol. 2005, 42, 928-940.
Friedman, J. M.; Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 1998, 395, 763-770.
Janeckova, R. The role of leptin in human physiology and pathophysiology. Physiol. Rev. 2001, 50, 443-459.
Munzberg, H.; Bjornholm, M.; Bates, S. H.; Myers, M. G., Jr. Leptin receptor action and mechanisms of leptin resistance. Cell Mol. Life Sci. 2005, 62, 642-652.
Zhang, Y.; Proenca, R.; Maffei, M.; Baronne, M.; Leopold, L.; Friedman, J. M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372, 425-432.
Tartaglia, L. A.; Dembski, M.; Weng, X.; Deng, N.; Culpepper, J.; Devos, R.; Richards, G. J.; Campfield, L. A.; Clark, F. T.; Deeds, J. Identification and expression cloning of a leptin receptor OBR. Cell 1995, 83, 1263-1271.
Ingalls, A. M.; Dickie, M. M.; Snell, G. D. Obese, new mutation in house mouse. J. Hered. 1950, 41, 317-318.
Lee, G. H.; Proenca, R.; Montez, J. M.; Carroll, K. M.; Darvishzadeh, J. G.; Lee, J. I.; Friedman, J. M. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996, 379, 632-635.
Wolf, G. Insulin resistance associated with leptin deficiency in mice: a possible model for noninsulin-dependent diabetes mellitus. Nutr. Rev. 2001, 59, 177-179.
Edvardsson, U.; Alexandersson, M.; Brockenhuus von Lowenhielm, H.; Nystrom, A.-C.; Ljung, B.; Nilsson, F.; Dahllof, B. A proteome analysis of livers from obese (ob/ob) mice treated with the peroxisome proliferators WY14, 643. Electrophoresis 1999, 20, 935-942.
Hookman, P.; Barkin, J. S. Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. Am. J. Gastroenterol. 2003, 98, 2093-2097.
Koteish, A.; Diehl, A. M. Animal models of steatohepatitis. Best Pract. Res. Clin. Gastroenterol. 2001, 16, 679-690.
Mootha, V. K.; Lepage, P.; Miller, K.; Bunkenborg, J.; Reich, M.; Hjerild, M.; Delmonte, T.; Villeneuve, A.; Sladek, R.; Xu, F.; Mitchell, G. A.; Morin, C.; Mann, M.; Hudson, T. J.; Robinson, B.; Rioux, J. D.; Lander, E. S. Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 605-610.
Görg, A.; Boguth, G.; Obermaier, C.; Posch, A.; Weiss, W. Two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimension (IPG-Dalt): the state of the art and the controversy of vertical versus horizontal systems. Electrophoresis 1995, 16, 1079-1086.
Shevchenko, A.; Wilm, M.; Vorm, O.; Mann, M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 1996, 68, 850-858.
Gharahdaghi, F.; Weinberg, C. R.; Meagher, D. A.; Imai, B. S.; Mische, S. M. Mass spectrometric identification of proteins from silver-stained polyacrylamide gel: a method for the removal of silver ions to enhance sensitivity. Electrophoresis 1999, 20, 601-605.
Alban, A.; David, S. O.; Bjorkesten, L.; Andersson, C.; Sloge, E.; Lewis, S.; Currie, I. A novel experimental design for comparative two-dimensional gel analysis: Two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 2003, 3, 36-44.
Knowles, M. R.; Cervino, S.; Skynner, H. A.; Hunt, S. P.; de Felipe, C.; Salim, K.; Meneses-Lorente, G.; McAllister, G.; Guest, P. C. Multiplex proteomic analysis by two-dimensional differential in-gel electrophoresis. Proteomics 2003, 3, 1162-1171.
Unlu, M.; Morgan, M. E.; Minden, J. S. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 1997, 18, 2071-2077.
Jiang, X.-S.; Dai, J.; Sheng, Q.-H.; Zhang, L; Xia, Q.-C.; Wu, J.-R.; Zeng R. A Comparative Proteomic Strategy for Subcellular Proteome Research. Mol. Cell. Proteomics 2005, 4, 12-34.
Gallegos, A. M.; Atshaves, B. P.; Storey, S. M.; Starodub, O.; Petrescu, A. D.; Huang, H.; McIntosh, A. L.; Martin, G. G.; Chao, H.; Kier, A. B.; Schroeder, F. Gene structure, intracellular localization and functional roles of sterol carrier protein-2. Prog. Lipid Res. 2001, 40, 498-563.
Brady, L. J.; Brady, P. S.; Romsos, R. D.; Hoppel, C. L. Elevated hepatic mitochondrial and peroxisomal oxidative capacities in fed and starved adult obese (ob/ob) mice. Biochem. J. 1985, 231, 439-444.
Sugden, M. C.; Bulmer, K.; Holness, M. J. Fuel-sensing mechanisms integrating lipid and carbohydrate utilization. Biochem. Soc. Trans. 2001, 29, 272-278.
Fromenty, D.; Robin, M. A.; Igougjil, A.; Mansouri, A.; Pessayre, D. The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab. 2004, 30, 121-138.
McIntyre, J. O.; Bock, H. G.; Fleischer, S. The orientation of D-beta-hydroxybutyrate dehydrogenase in the mitochondrial inner membrane. Biochim. Biophys. Acta 1978, 513, 255-267.
Gorg, A.; Weiss, W.; Dunn, M. J. Current two-dimensional electrophoresis technology for proteomics. Proteomics 2004, 4, 3665-3685.
Bailey, S. M.; Landar, A.; Darley-Usmar, V. Mitochondrial proteomics in free radical research. Free Radic. Biol. Med. 2005, 38, 175-188.
Chavin, K. D.; Yang, S. Q.; Lin, H. Z.; Chatham, J.; Chacko, V. P.; Hoek, J. B.; Walajtys-Rode, E.; Rashid, A.; Chen, C.-H.; Huang, C.-C; Wu, T.-C.; Lane, M. D.; Diehl, A. M. Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J. Biol. Chem. 1999, 274, 5692-5700.
Vidal-Puig, A. J. Uncoupling expectations. Nat. Genet. 2000, 25, 387-388.
Yang, S. Q.; Zhu, H.; Li, Y.; Lin, H. Z.; Gabrielson, K.; Trush, M. A.; Diehl, A. M. Mitochondrial adaptation to obesity-related oxidant stress. Arch. Biochem. Biophys. 2000, 378, 259-268.
Lee, S. M.; Koh, H. J.; Park, D. C.; Song, B. J.; Huh, T. L.; Park, J. W. Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radic. Biol. Med. 2002, 32, 1185-1196.
Fountoulakis, M.; Berndt, P.; Langen, H.; Suter, L. The rat liver mitochondrial proteome. Electrophoresis 2002, 23, 311-328.
Murphy, T. C.; Amarnath, V.; Gibson, K. M.; Picklo, M. J., Sr. Oxidation of 4-hydroxy-2-nonenal by succinic semialdehyde dehydrogenase (ALDH5A). J. Neurochem. 2003, 86, 298-305.
Vasiliou, V.; Pappa, A. Polymorphisms of human aldehyde dehydrogenases. Pharmacology 2000, 61, 192-198.
Verniquet, F.; Gaillard, J.; Neuburger, M.; Douce, R. Rapid inactivation of plant aconitase by hydrogen peroxide. Biochem. J. 1991, 276, 643-648.
Venkatraman, A.; Landar, A.; Davis, A. J.; Chamlee, L.; Sanderson, T.; Kim, H.; Page, G.; Pompilius, M.; Ballinger, S.; Darley-Usmar, V.; Bailey, S. M. Modification of the mitochondrial proteome in response to stress of ethanol-dependent hepatotoxicity. J. Biol. Chem. 2004, 279, 22092-22101.
