Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome.
Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome.
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DOI：
10.1155/2012/962183
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发表时间：
2012
影响因子：
1.8
通讯作者：
Bailey SM
中科院分区：
文献类型：
--
作者：
Kharbanda KK;Todero SL;King AL;Osna NA;McVicker BL;Tuma DJ;Wisecarver JL;Bailey SM
导论.线粒体损伤和氧化磷酸化的破坏是酒精性肝损伤的发病机制之一。在此，我们测试了甜菜碱对酒精性肝损伤的肝保护作用发生在线粒体蛋白质组水平的假设。方法.雄性Wister大鼠配对喂养对照或含乙醇的液体饲料补充或不补充甜菜碱（10 mg/mL）4-5 wks. Liver检查甘油三酯的积累，蛋氨酸循环代谢产物的水平，和线粒体蛋白的改变。结果慢性乙醇摄入导致甘油三酯的积累，这是衰减乙醇加甜菜碱组。蓝色天然凝胶电泳（BN-PAGE）显示，乙醇喂养的动物线粒体中完整的氧化磷酸化复合物的含量显着下降。甜菜碱的补充防止了许多低分子量氧化磷酸化蛋白的酒精依赖性损失。甜菜碱的这种保护作用与SAM：S-腺苷高半胱氨酸（SAH）比值的正常化以及乙醇诱导的诱导型一氧化氮合酶和肝脏一氧化氮生成增加的衰减有关。讨论/结论。总之，甜菜碱减弱酒精性脂肪变性和氧化磷酸化系统的改变。因此，线粒体功能的保护可能是甜菜碱保护肝脏的另一个关键分子机制。
Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection.