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-beta1 (TGF-beta1) in mouse hepatocytes. Inhibition of AMPK by Compound C, a selective AMPK-alpha inhibitor, inhibited TGF-beta1-induced apoptosis and EMT in hepatocytes. In addition, overexpression of a dominant-negative form of AMPK-alpha subunit also suppressed TGF-beta1-induced EMT and apoptosis in AML12 cells. Furthermore, inhibition of AMPK suppressed TGF-beta1-induced Smad3 transcriptional activity. This study indicates that AMPK is able to modulate Smad3 transcriptional activity, which plays an important role in TGF-beta1-induced apoptosis and EMT.
Wang
Xunde
X
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Pan
Xinchao
X
Song
Jianguo
J
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D022781:Hepatocytes / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D011720:Pyrazoles; D011743:Pyrimidines; D034741:RNA, Small Interfering; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; C516138:dorsomorphin; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases