Proteomic profile of carbonylated proteins in rat liver: Discovering possible mechanisms for tetracycline-induced steatosis
Proteomic profile of carbonylated proteins in rat liver: Discovering possible mechanisms for tetracycline-induced steatosis
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DOI：
10.1002/pmic.201400115
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发表时间：
2015-01-01
期刊：
影响因子：
3.4
通讯作者：
Li, Guolin
中科院分区：
文献类型：
--
作者：
Deng, Zhenglu;Yan, Siyu;Li, Guolin
为了研究四环素诱导的大鼠脂肪变性的生化机制，对氧化修饰的靶蛋白进行了分析。结果表明，四环素诱导的脂质积累，氧化应激和细胞活力下降的HepG 2细胞只有在棕榈酸过载的情况下。四环素可使大鼠血脂显著降低，但肝内甘油三酯升高4倍以上，肝脏出现典型的微泡性脂肪变性。三酰甘油水平与氧化应激呈正相关。羰基化蛋白的蛋白质组学图谱显示，26个目标蛋白易受氧化修饰，其中大部分位于线粒体。其中，长链特异性酰基辅酶A脱氢酶是调节脂肪酸β-氧化的关键酶之一。四环素组中酶的氧化修饰抑制其酶活性。总之，增加流入肝脏的脂质是四环素诱导的微泡性脂肪变性的第一击。氧化应激是二次打击的重要组成部分，它可能是由于脂质过载而产生的，并攻击一系列功能蛋白，加重脂肪变性的发展。本文揭示的26种靶蛋白提供了氧化应激和四环素诱导的脂肪变性之间的潜在直接联系。
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 beta-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.