Impact of chronic alcohol ingestion on cardiac muscle protein expression.

Impact of chronic alcohol ingestion on cardiac muscle protein expression.
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DOI:
10.1111/j.1530-0277.2010.01200.x
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发表时间:
2010-07
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Vary TC
Vary TC
中科院分区:
其他
文献类型:
--
作者:
Fogle RL;Lynch CJ;Palopoli M;Deiter G;Stanley BA;Vary TC

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长期酗酒不仅会增加与健康有关的并发症的风险,而且会导致成年人过早死亡。心肌功能障碍,包括酒精性心肌病综合征的发展,似乎是一个主要的促成因素。解释酒精性心肌病发病机制的一种机制涉及继发于蛋白质合成抑制的蛋白质表达改变。然而,心肌蛋白受慢性饮酒影响的程度仍然没有得到解决。本研究的目的是研究慢性饮酒对心脏蛋白表达的影响。雄性大鼠维持16周的含40%乙醇的饮食,其中酒精提供饮用水和琼脂块。对照组动物成对喂养,以消耗相同的热量摄入。用可裂解同位素编码的亲和标签(ICAT™)标记来自对照和乙醇喂养的大鼠的心脏匀浆。在与ICAT™试剂反应后,我们应用一维凝胶电泳和蛋白质的凝胶内胰蛋白酶消化,以及随后的MALDI-TOF-TOF质谱技术来鉴定肽。通过质谱法测定了对照组和乙醇组大鼠心脏蛋白表达的差异。初步的蛋白质组学分析鉴定并定量了数百种心脏蛋白。观察到特异性心肌蛋白表达的显著降低。蛋白质根据其对心脏功能和代谢的多种活动的贡献进行分组,包括线粒体蛋白、糖酵解蛋白、肌原纤维蛋白、膜相关蛋白和血浆蛋白。另一组包含无法根据上述分类系统正确分类的已鉴定蛋白质。基于蛋白质的变化,我们推测心肌蛋白质表达的调节代表了慢性饮酒引起的根本性改变,与在相同条件下测量的心肌壁厚度的变化一致。
Chronic alcohol abuse contributes not only to an increased risk of health-related complications, but also to a premature mortality in adults. Myocardial dysfunction, including the development of a syndrome referred to as alcoholic cardiomyopathy, appears to be a major contributing factor. One mechanism to account for the pathogenesis of alcoholic cardiomyopathy involves alterations in protein expression secondary to an inhibition of protein synthesis. However, the full extent to which myocardial proteins are affected by chronic alcohol consumption remains unresolved. The purpose of this study was to examine the effect of chronic alcohol consumption on the expression of cardiac proteins. Male rats were maintained for 16 weeks on a 40% ethanol-containing diet in which alcohol was provided both in drinking water and agar blocks. Control animals were pair-fed to consume the same caloric intake. Heart homogenates from control- and ethanol-fed rats were labeled with the cleavable isotope coded affinity tags (ICAT™). Following the reaction with the ICAT™ reagent, we applied one-dimensional gel electrophoresis with in-gel trypsin digestion of proteins and subsequent MALDI-TOF-TOF mass spectrometric techniques for identification of peptides. Differences in the expression of cardiac proteins from control- and ethanol-fed rats were determined by mass spectrometry approaches. Initial proteomic analysis identified and quantified hundreds of cardiac proteins. Major decreases in the expression of specific myocardial proteins were observed. Proteins were grouped depending on their contribution to multiple activities of cardiac function and metabolism, including mitochondrial-, glycolytic-, myofibrillar-, membrane-associated, and plasma proteins. Another group contained identified proteins that could not be properly categorized under the aforementioned classification system. Based on the changes in proteins, we speculate modulation of cardiac muscle protein expression represents a fundamental alteration induced by chronic alcohol consumption, consistent with changes in myocardial wall thickness measured under the same conditions.
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