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-α can be activated by transforming growth factor-β1 (...

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Bibliographic Details
Published in:Cellular signalling 2010-11, Vol.22 (11), p.1790-1797
Main Authors: Wang, Xunde, Pan, Xinchao, Song, Jianguo
Format: Article
Language:English
Subjects:
AMP-activated protein kinase
AMP-Activated Protein Kinases - antagonists & inhibitors
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
Animals
Apoptosis
Cellular
Control
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelial-Mesenchymal Transition
Epithelial-to-mesenchymal transition
Hepatocytes - metabolism
Homeostasis
Inhibition
Inhibitors
Kinases
Mesoderm - cytology
Mesoderm - metabolism
Mice
Proteins
Pyrazoles - pharmacology
Pyrimidines - pharmacology
RNA Interference
RNA, Small Interfering - metabolism
Smad3 Protein - genetics
Smad3 Protein - metabolism
TGF-beta
Transforming Growth Factor beta1 - metabolism
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Summary: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-α can be activated by transforming growth factor-β1 (TGF-β1) in mouse hepatocytes. Inhibition of AMPK by Compound C, a selective AMPK-α inhibitor, inhibited TGF-β1-induced apoptosis and EMT in hepatocytes. In addition, overexpression of a dominant-negative form of AMPK-α subunit also suppressed TGF-β1-induced EMT and apoptosis in AML12 cells. Furthermore, inhibition of AMPK suppressed TGF-β1-induced Smad3 transcriptional activity. This study indicates that AMPK is able to modulate Smad3 transcriptional activity, which plays an important role in TGF-β1-induced apoptosis and EMT.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2010.07.008