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Extracellular signal‐regulated kinase (ERK) participates in the hypercapnia‐induced Na,K‐ATPase downregulation
Author(s) -
Welch Lynn C.,
Lecuona Emilia,
Briva Arturo,
Trejo Humberto E.,
Dada Laura A.,
Sznajder Jacob I.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.08.002
Subject(s) - hypercapnia , mapk/erk pathway , microbiology and biotechnology , endocytosis , extracellular , chemistry , reabsorption , downregulation and upregulation , ouabain , protein kinase a , kinase , medicine , endocrinology , biology , biochemistry , respiratory system , sodium , cell , organic chemistry , gene , kidney
Hypercapnia has been shown to impair alveolar fluid reabsorption (AFR) by decreasing Na,K‐ATPase activity. Extracellular signal‐regulated kinase pathway (ERK) is activated under conditions of cellular stress and has been known to regulate the Na,K‐ATPase. Here, we show that hypercapnia leads to ERK activation in a time‐dependent manner in alveolar epithelial cells (AEC). Inhibition of ERK by U0126 or siRNA prevented both the hypercapnia‐induced Na,K‐ATPase endocytosis and impairment of AFR. Moreover, ERK inhibition prevented AMPK activation, a known modulator of hypercapnia‐induced Na,K‐ATPase endocytosis. Accordingly, these data suggest that hypercapnia‐induced Na,K‐ATPase endocytosis is dependent on ERK activation in AEC and that ERK plays an important role in hypercapnia‐induced impairment of AFR in rat lungs.