HDMCP uncouples yeast mitochondrial respiration and alleviates steatosis in L02 and hepG2 cells by decreasing ATP and H2O2 levels: a novel mechanism for NAFLD
| Autor: | Lin Zheng, Zhiyuan Lv, Shao-hua Chen, Yaping Liu, Cheng-yu Zhang, Chaohui Yu, Xi Jin, Xue-yuan Jiang, Youming Li, Yida Yang, Kun Chen |
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| Rok vydání: | 2008 |
| Předmět: |
Carcinoma
Hepatocellular Molecular Sequence Data Mitochondrion Mitochondrial Membrane Transport Proteins Ion Channels Cell Line Mitochondrial Proteins Rats Sprague-Dawley Mitochondrial membrane transport protein Adenosine Triphosphate RNA interference Cell Line Tumor medicine Uncoupling protein Animals Humans Amino Acid Sequence Uncoupling Protein 1 Hepatology biology Fatty liver Liver Neoplasms Membrane Transport Proteins Hydrogen Peroxide medicine.disease Mitochondrial carrier Thermogenin Rats Fatty Liver Disease Models Animal Biochemistry biology.protein Hepatocytes Steatosis |
| Zdroj: | Journal of hepatology. 50(5) |
| ISSN: | 1600-0641 |
| Popis: | Background/Aims To explore the uncoupling activity of hepatocelluar downregulated mitochondrial carrier protein (HDMCP) in a yeast expression system and its function in non-alcoholic fatty liver disease (NAFLD). Methods Molecular cloning and RT-PCR were used for yeast protein expression and uncoupling activity was assessed. Western blot analysis was used to determine HDMCP level in rat NAFLD and steatotic L02 and hepG2 cell models where their presence was confirmed by pathologic (Nile red and H-E staining) and biochemical changes. RNA interference was used to knock down HDMCP level and mitochondrial ATP and hydroperoxide levels were measured for potential mechanism exploration. Results We found a significant GDP insensitive uncoupling activity of HDMCP in yeast mitochondria and its increased expression in animal and cell models. HDMCP was significantly increased with culture time and steatosis was aggravated when HDMCP level was knocked down. Furthermore, we found that HDMCP might function through promoting ATP depletion and decreasing H 2 O 2 production. Conclusion This study adds supportive data to the hypothesis that HDMCP might be a long postulated liver-specific uncoupling protein and broadens our understanding of the pathogenesis of NAFLD. More importantly, HDMCP might become a novel drug target for its ability in alleviating hepatic steatosis. |
| Databáze: | OpenAIRE |
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