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Cigarette smoke condensate inhibits expression of ENaC α‐subunit in lung epithelial cells
Author(s) -
Chu Shijian,
Xu Haishan,
Ferro Thomas J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a549-a
Subject(s) - epithelial sodium channel , lung , oxidative stress , chemistry , inflammation , cigarette smoke , amiloride , smoke , cancer research , microbiology and biotechnology , immunology , medicine , biology , biochemistry , sodium , toxicology , organic chemistry
Cigarette smoke causes inflammatory lung diseases and lung epithelial damage. The amiloride‐sensitive epithelial sodium channel ENaC plays an important role in the regulation of lung fluid transport. We hypothesized that at the early stage of cigarette smoke‐induced lung epithelial damage, dysfunctional ENaC leads to inefficient lung fluid absorption, predisposing smoker lungs to repeated inflammation and episodes of acute lung injury. To test this hypothesis, we examined expression of α‐subunit of ENaC in human lung epithelial cell H441. Splice variant 2 of the α‐subunit (α2) is the predominant variant in H441 cells and is co‐expressed with α1 in human lung. The α2 variant possesses channel functions similar to α1, and is expressed from a unique promoter. Using quantitative RT‐PCR, we found cigarette smoke condensate (CSC) inhibits α2 expression in a dose‐dependent manner. Same trend was seen in α2 promoter activity in H441 cells treated with CSC. As cigarette smoke induces oxidative stress in lungs, we tested possible effects of oxidative stress on α2 expression. Our results show in H441 cells that (1) CSC induces H 2 O 2 production, (2) H 2 O 2 suppresses α2 expression, and (3) antioxidants reduce CSC‐induced inhibition of α2 expression. These results suggest that cigarette smoke inhibits expression of ENaC α‐subunit in lung epithelial cells through increased oxidative stress.