title: Proteomic profile of carbonylated proteins in rat liver: discovering possible mechanisms for tetracycline-induced steatosis.
abstract: To investigate biochemical mechanisms for the tetracycline-induced steatosis in rats, targeted proteins of oxidative modification were profiled. The results showed that tetracycline induced lipid accumulation, oxidative stress, and cell viability decline in HepG2 cells only under the circumstances of palmitic acid overload. Tetracycline administration in rats led to significant decrement in blood lipids, while resulted in more than four times increment in intrahepatic triacylglycerol and typical microvesicular steatosis in the livers. The triacylglycerol levels were positively correlated with oxidative stress. Proteomic profiles of carbonylated proteins revealed 26 targeted proteins susceptible to oxidative modification and most of them located in mitochondria. Among them, the long-chain specific acyl-CoA dehydrogenase was one of the key enzymes regulating fatty acid β-oxidation. Oxidative modification of the enzyme in the tetracycline group depressed its enzymatic activity. In conclusion, the increased influx of lipid into the livers is the first hit of tetracycline-induced microvesicular steatosis. Oxidative stress is an essential part of the second hit, which may arise from the lipid overload and attack a series of functional proteins, aggravating the development of steatosis. The 26 targeted proteins revealed here provide a potential direct link between oxidative stress and tetracycline-induced steatosis.
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, P. R. China.
authors.forename: Zhenglu
authors.initials: Z
authors.lastname: Deng
authors.forename: Siyu
authors.initials: S
authors.lastname: Yan
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.forename: Zhigui
authors.initials: Z
authors.lastname: Duan
authors.forename: Lanxuan
authors.initials: L
authors.lastname: Yin
authors.forename: Shenke
authors.initials: S
authors.lastname: Liao
authors.forename: Yubai
authors.initials: Y
authors.lastname: Sun
authors.forename: Dazhong
authors.initials: D
authors.lastname: Yin
authors.forename: Guolin
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D050050:Protein Carbonylation; D060066:Protein Interaction Maps; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013752:Tetracycline
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D011506:Proteins; D013752:Tetracycline
keywords: Animal proteomics; Carbonylation; Nonalcoholic fatty liver disease (NAFLD); Oxidative stress; Rat; Tetracycline