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首页> 外文期刊>American Journal of Physiology >Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species
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Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

机译：乙醇通过增加活性氧来刺激上皮钠通道

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摘要

Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (Fo) and the number of active ENaC in patches (JV). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased alpha-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hy-droxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde.
机译：酒精会影响人体钠平衡，但其分子机制尚不清楚。我们使用单通道方法检查乙醇如何影响A6远端肾细胞中的上皮钠通道（ENaC）。数据显示，乙醇显着增加了ENaC的开放概率（Fo）和斑块中有效ENaC的数量（JV）。 1-丙醇和1-丁醇也可提高ENaC活性，但异醇则不能。乙醇的作用被乙醛（乙醇的第一个代谢产物）模仿，但没有被丙酮（2-丙醇的代谢产物）模仿。共聚焦显微镜和表面生物素化显示，除了增加打开通道的可能性和活跃通道的表观密度外，乙醇还显着增加了顶膜中的α-ENaC蛋白。乙醇对ENaC Po和N的影响已被超氧化物清除剂4-hy-droxy-2,2,6,6-四甲基哌啶基氧基（TEMPOL）消除，并被磷脂酰肌醇3-激酶抑制剂LY294002阻断。与乙醇诱导的活性氧（ROS）对ENaC的影响一致，伯醇和乙醛会升高细胞内ROS，而仲醇却没有。结合我们先前对ROS刺激ENaC的发现，目前的结果表明，乙醇可能通过其代谢产物乙醛升高细胞内ROS来刺激ENaC。

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