AMP-activated protein kinase is required for induction of apoptosis and epithelial-to-mesenchymal transition

AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which has been implicated in the regulation of cellular energy homeostasis. Relatively very little is known about its role in other cellular processes. We observed that AMPK-alpha can be activated by transforming growth factor-beta 1 (TGF-beta 1) in mouse hepatocytes. Inhibition of AMPK by Compound C, a selective AMPK-alpha inhibitor, inhibited TGF-beta 1-induced apoptosis and EMT in hepatocytes. In addition, overexpression of a dominant-negative form of AMPK-alpha subunit also suppressed TGF-beta 1-induced EMT and apoptosis in AML12 cells. Furthermore, inhibition of AMPK suppressed TGF-beta 1-induced Smad3 transcriptional activity. This study indicates that AMPK is able to modulate Smad3 transcriptional activity, which plays an important role in TGF-beta 1-induced apoptosis and EMT. (C) 2010 Elsevier Inc. All rights reserved.