Sex-dependent differences in the regulation of myocardial protein synthesis following long-term ethanol consumption.
Sex-dependent differences in the regulation of myocardial protein synthesis following long-term ethanol consumption.
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DOI：
10.1152/ajpregu.00203.2006
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发表时间：
2007-02
期刊：
影响因子：
--
通讯作者：
T. Vary;S. Kimball;A. Sumner
中科院分区：
文献类型：
--
作者：
T. Vary;S. Kimball;A. Sumner
长期大量饮酒会改变心脏结构和功能。关于女性心脏是否以类似于男性的方式对长期乙醇摄入做出反应，仍存在争议。特别是，心肌对长期饮酒的反应的性别差异在分子水平上仍未得到解决。本组实验的目的是确定长期饮酒 26 周后心脏结构和蛋白质代谢的变化是否表现出性别二态性。在对照动物中，与雄性大鼠相比，雌性大鼠的心脏显示出较低的心脏重量和更薄的心室壁。较小的心脏尺寸与较低的蛋白质含量相关，部分原因是蛋白质合成率降低。根据超声心动图评估，男性长期饮酒会导致心室壁和室内间隔变薄，而女性则不会，这与心脏质量的损失相关。心脏大小的改变部分是通过蛋白质合成率降低导致的蛋白质含量降低而发生的。蛋白质合成速率的降低似乎与活性真核起始因子 (eIF)4G.eIF4E 复合物组装减少有关，继发于 eIF4G 磷酸化减少和无活性 4E 结合蛋白 (4EBP1).eIF4E 复合物形成增加。后一种效应是由于 4EBP1 磷酸化减少而发生的。在女性心脏中没有观察到这些乙醇引起的男性心脏变化。这些数据表明，慢性酒精引起的心肌蛋白质合成损伤部分是由于男性 eIF4E.eIF4G 复合物形成显着减少所致。食用乙醇的雌性大鼠未能表现出结构变化似乎与乙醇无法像雄性大鼠那样影响调节蛋白质合成的程度有关。
Chronic heavy alcohol consumption alters cardiac structure and function. Controversies remain as to whether hearts from females respond to the chronic ethanol intake in a manner analogous to males. In particular, sex differences in the myocardial response to chronic alcohol consumption remain unresolved at the molecular level. The purpose of the present set of experiments was to determine whether alterations in cardiac structure and protein metabolism show sexual dimorphism following chronic alcohol consumption for 26 wk. In control animals, hearts from female rats showed lowered heart weights and had thinner ventricular walls compared with males. The smaller heart size was associated with a lower protein content that occurred in part from a reduced rate of protein synthesis. Chronic alcohol consumption in males, but not in females, caused a thinning of the ventricular wall and intraventricular septum, as assessed by echocardiography, correlating with the loss of heart mass. The alterations in cardiac size occurred, in part, through a lowering of the protein content secondary to a diminished rate of protein synthesis. The decreased rate of protein synthesis appeared related to a reduced assembly of active eukaryotic initiation factor (eIF)4G.eIF4E complex secondary to both a diminished phosphorylation of eIF4G and increased formation of inactive 4Ebinding protein (4EBP1).eIF4E complex. The latter effects occurred as a result of decreased phosphorylation of 4EBP1. None of these ethanol-induced alterations in hearts from males were observed in hearts from females. These data suggest that chronic alcohol-induced impairments in myocardial protein synthesis results, in part, from marked decreases in eIF4E.eIF4G complex formation in males. The failure of female rats consuming ethanol to show structural changes appears related to the inability of ethanol to affect the regulation protein synthesis to the same extent as their male counterparts.