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首页> 外文期刊>American Journal of Physiology >Analysis of the liver mitochondrial proteome in response to ethanol and S-adenosylmethionine treatments: Novel molecular targets of disease and hepatoprotection
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Analysis of the liver mitochondrial proteome in response to ethanol and S-adenosylmethionine treatments: Novel molecular targets of disease and hepatoprotection

机译：乙醇和S-腺苷甲硫氨酸治疗对肝脏线粒体蛋白质组的分析：疾病和保肝的新分子靶标

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摘要

S-adenosylmethionine (SAM) minimizes alcohol hepatotoxicity; however, the molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein, we use proteomics to determine whether the hepatoprotective action of SAM against early-stage alcoholic liver disease is linked to alterations in the mitochondrial proteome. For this, male rats were fed control or ethanol-containing liquid diets ± SAM and liver mitochondria were prepared for proteomic analysis. Two-dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative phosphorylation (OxPhos) proteins, respectively. SAM coadministration minimized alcohol-dependent inflammation and preserved mitochondrial respiration. SAM supplementation preserved liver SAM levels in ethanol-fed rats; however, mitochondrial SAM levels were increased by ethanol and SAM treatments. With use of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in response to ethanol, SAM, or both. Classes of proteins affected by ethanol and SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the proteome were not linked to corresponding changes in gene expression. In conclusion, ethanol and SAM treatment led to multiple changes in the liver mitochondrial proteome. The protective effects of SAM against alcohol toxicity are mediated, in part, through maintenance of proteins involved in key mitochondrial energy conserving and biosynthetic pathways. This study demonstrates that SAM may be a promising candidate for treatment of alcoholic liver disease.
机译：S-腺苷甲硫氨酸（SAM）可以最大程度地降低酒精肝毒性;然而，负责SAM肝保护的分子机制仍然未知。在本文中，我们使用蛋白质组学来确定SAM对早期酒精性肝病的保肝作用是否与线粒体蛋白质组的改变有关。为此，给雄性大鼠喂食对照或含乙醇的流质饮食±SAM，并准备肝线粒体用于蛋白质组学分析。二维等电聚焦（2D IEF / SDS-PAGE）和蓝色天然凝胶电泳（BN-PAGE）分别用于确定基质和氧化磷酸化（OxPhos）蛋白的变化。 SAM共同给药可最大程度地减少酒精依赖性炎症并保持线粒体呼吸。补充SAM可以维持以乙醇喂养的大鼠的肝脏SAM水平。然而，乙醇和SAM处理可增加线粒体SAM水平。使用2D IEF / SDS-PAGE时，响应乙醇，SAM或两者，30种蛋白质的丰度发生了显着变化。受乙醇和SAM处理影响的蛋白质类别包括伴侣蛋白，β氧化蛋白，硫代谢蛋白和涉及蛋氨酸，甘氨酸和胆碱代谢的脱氢酶。 BN-PAGE揭示了响应乙醇，SAM或两者的19种OxPhos蛋白水平发生了新变化。蛋白质组中乙醇和SAM依赖的变化与基因表达的相应变化无关。总之，乙醇和SAM的治疗导致肝脏线粒体蛋白质组发生多种变化。 SAM对酒精毒性的保护作用部分是通过维持参与关键线粒体能量守恒和生物合成途径的蛋白质来介导的。这项研究表明，SAM可能是治疗酒精性肝病的有前途的候选人。

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