Adenosine monophosphate kinase (AMPK) and cell‐cell adhesion: a role for AMPK in pulmonary microvascular endothelial barrier function

Abstract

In the lung, efficient gas exchange relies on the dynamic interaction of cell‐cell tethering mechanisms to maintain capillary barrier integrity. AMPK is a molecular sensor for detecting and mediating cellular adaptation to barrier disruptive stimuli. However, the importance of AMPK activity in mediating pulmonary microvascular endothelial barrier function is not well understood. Initial studies reveal that pulmonary microvascular endothelial cells (PMVECs) selectively express the alpha 1 and not the alpha 2 isoform of the AMPK catalytic subunit. AMPK inhibition blocked PMVEC growth on matrigel. In scratch wound assays inhibition of AMPK by compound C or shRNA to AMPK alpha 1 attenuated PMVEC monolayer resealing. Transendothelial resistance studies revealed that shRNA‐induced knockdown of AMPK alpha 1 expression decreased resistance in confluent monolayers by 35%. Immunochemical staining and co‐immunoprecipitation indicated that AMPK alpha 1 co‐localizes with the cell‐cell adhesion molecule N‐cadherin. Moreover, fractionation studies revealed that membrane associated AMPK alpha 1 and N‐cadherin are restricted to lipid raft membranes with caveolin 1. Collectively, these data suggest that AMPK alpha 1 interaction with N‐cadherin contributes to cell‐cell contact important in barrier repair . Supported by research and training grants from NIH.