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Adenosine monophosphate kinase (AMPK) expression and activity in the lung
Author(s) -
Creighton Judy,
Insel Paul
Publication year - 2008
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.22.1_supplement.928.4
Subject(s) - ampk , microbiology and biotechnology , protein kinase a , hypoxia (environmental) , amp activated protein kinase , gene isoform , cell growth , chemistry , cell , biology , kinase , biochemistry , gene , organic chemistry , oxygen
AMPK activity has been implicated in endothelial cell death and vascular smooth muscle proliferation in hypoxia, suggesting that this metabolic sensor participates in vascular pathology. However, molecular mechanisms of AMPK signaling in the lung are poorly understood. Initial studies revealed that the 2 isoforms of AMPK (AMPKα1 and AMPKα2) are expressed at low levels in the rat lung but that hypoxia induces AMPK expression in an isoform‐ and location‐dependent manner. AMPKα1 expression is predominantly induced in the lung periphery and is associated with capillaries while AMPKα2 is expressed in larger vessels. Selective expression of AMPK isoforms extends to distinct pulmonary cell types: pulmonary artery endothelial cells (PAECs) express AMPKα2 while pulmonary microvascular endothelial cells (PMVECs) express AMPKα1. Smooth muscle cells (SMCs) and columnar epithelia express both isoforms. Studies using PAEC, PMVEC, and SMC cultures revealed that AMPK inhibition increases SMC growth and attenuates PMVEC growth. Immunochemical staining indicated that AMPK α1 co‐localizes with the cell adhesion molecule N‐cadherin near regions of cell‐cell contact in PMVECs, results confirmed in co‐immunoprecipitation assays. In conclusion, AMPK expression and function in the lung exhibits both isoform and cell‐type specificity. Supported by research and training grants from NIH.