ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress.

ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress. Research Abstract Details 

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ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress. Abstract Text:

Haishan Xu,Shijian Chu,Haishan Xu,Shijian Chu,Haishan Xu,Shijian Chu,

Amiloride-sensitive epithelial sodium channel (ENaC) is a major sodium channel in the lung facilitating fluid absorption. ENaC is composed of alpha-, beta-, and gamma-subunits, and the alpha-subunit is indispensable for ENaC function in the lung. In human lungs, the alpha-subunit is expressed as various splice variants. Among them, alpha(1)- and alpha(2)-subunits are two major variants with different upstream regulatory sequences that possess similar channel characteristics when tested in Xenopus oocytes. Despite the importance of alpha-ENaC, little was known about the relative abundance of its variants in lung epithelial cells. Furthermore, lung infection and inflammation are often accompanied by reduced alpha-ENaC expression, oxidative stress, and pulmonary edema. However, it was not clear how oxidative stress affects expression of alpha-ENaC variants. In this study, we examined relative expression levels of alpha-subunit variants in four human lung epithelial cell lines. We also tested the hypothesis that oxidative stress inhibits alpha-ENaC expression. Our results show that both alpha(1)- and alpha(2)-ENaC variants are expressed in the cells we tested, but relative abundance varies. In the two monolayer-forming cell lines, H441 and Calu-3, alpha(2)-ENaC is the predominant variant. We also show that H(2)O(2) specifically suppresses alpha(1)- and alpha(2)-ENaC variant expression in H441 and Calu-3 cells in a dose-dependent fashion. This suppression is achieved by inhibition of their promoters and is attenuated by dexamethasone. These data demonstrate the importance of the alpha(2)-subunit variant and suggest that glucocorticoids and antioxidants may be useful in correcting infection/inflammation-induced lung fluid imbalance.

ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress. Publishing Authors By Initials

H Xu,S Chu,H Xu,S Chu,H Xu,S Chu,

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ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Lung cellular and

VOLUME: 293

Page Numbers: L1454-62

Journal Abbreviation: Am. J. Physiol. Lung Cell Mol.

ISSN: 1040-0605

DAY: 28

MONTH: 09

YEAR: 2007

ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress. Information

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LANGUAGE: eng

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Grant and Affiliation Information for ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress.

AFFILIATION: McGuire Veterans Affairs Medical Center (151 1201 Broad Rock Blvd., Richmond, VA 23249. schu@vcu.edu).

Country: United States

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MEDLINETA: Am J Physiol Lung Cell Mol Phy

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