Ethanol alters alveolar fluid balance via Nadph oxidase (NOX) signaling to epithelial sodium channels (ENaC) in the lung.
Ethanol alters alveolar fluid balance via Nadph oxidase (NOX) signaling to epithelial sodium channels (ENaC) in the lung.
复制标题
DOI：
10.1371/journal.pone.0054750
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Helms MN
中科院分区：
文献类型：
--
作者：
Downs CA;Trac DQ;Kreiner LH;Eaton AF;Johnson NM;Brown LA;Helms MN
长期饮酒与ICU相关发病率和死亡率的增加有关，主要是急性呼吸窘迫综合征(ARDS)。然而，其中涉及的机制尚不清楚。一种解释是酒精通过氧化剂信号调节上皮钠通道(ENaC)，以促进促进损伤的环境。我们使用小型啮齿动物模型来模拟急性和慢性饮酒，并验证了乙醇(Etoh)通过上调肺内ENaC活性来影响肺液清除的假设。对大鼠肺切片和活体小鼠肺的荧光标记显示，急性乙醇暴露后ROS产生增加。用免疫印迹和5-马来酰亚胺荧光素标记，我们得出结论：乙醇暴露改变了α-eNaC的半胱氨酸，而单通道膜片钳分析数据证实，0.16%的乙醇能增加大鼠肺泡细胞eNaC的活性。在活体内，接受乙醇饮食的小鼠的肺液清除量显示出潜在的液体清除量增加。与热量对照组小鼠和C57BL/6小鼠相比，给予内毒素气管滴注的乙醇小鼠表现出更早的肺液清除。标准的生化技术表明，长期摄入乙醇会导致催化gp91Phox亚单位和专有的rac1蛋白的蛋白表达增加。总而言之，这些数据表明，长期摄入乙醇可能会导致ENaC的调节发生变化，从而导致酒精肺的“促损伤”环境。
Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS). However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC) via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH) would affect lung fluid clearance by up-regulating ENaC activity in the lung. Fluorescence labeling of rat lung slices and in vivo mouse lung revealed an increase in ROS production in response to acute EtOH exposure. Using western blots and fluorescein-5-maleimide labeling, we conclude that EtOH exposure modifies cysteines of α-ENaC while data from single channel patch clamp analysis confirm that 0.16% EtOH increased ENaC activity in rat alveolar cells. In vivo lung fluid clearance demonstrated a latent increase in fluid clearance in mice receiving EtOH diet. Ethanol mice given a tracheal instillation of LPS demonstrated early lung fluid clearance compared to caloric control mice and C57Bl/6 mice. Standard biochemical techniques reveal that chronic EtOH consumption resulted in greater protein expression of the catalytic gp91phox subunit and the obligate Rac1 protein. Collectively these data suggest that chronic EtOH consumption may lead to altered regulation of ENaC, contributing to a ‘pro-injury’ environment in the alcohol lung.
登录
查看更多内容
DOI：
10.3791/1941
发表时间：
2010-08-29
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Helms, My N;Torres-Gonzalez, Edilson;Rojas, Mauricio
通讯作者：
Rojas, Mauricio
影响因子：
5.5
作者：
Fink, B;Laude, K;Dikalov, S
通讯作者：
Dikalov, S
DOI：
10.1152/ajplung.00038.2012
发表时间：
2012-06-01
影响因子：
4.9
作者：
Downs, Charles A.;Kriener, Lisa H.;Helms, My N.
通讯作者：
Helms, My N.
DOI：
10.1152/ajplung.00408.2006
发表时间：
2007-05-01
影响因子：
4.9
作者：
Li, Xiaoling;Kovacs, Elizabeth J.;Choudhry, Mashkoor A.
通讯作者：
Choudhry, Mashkoor A.
DOI：
10.1152/ajplung.00260.2011
发表时间：
2012-02-01
影响因子：
4.9
作者：
Goodson, Preston;Kumar, Amrita;Helms, My N.
通讯作者：
Helms, My N.