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

Xunde Wang; Xinchao Pan; Jianguo Song

doi:10.1016/j.cellsig.2010.07.008

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

Xunde Wang, Xinchao Pan, Jianguo Song

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1790-1797
Number of pages	8
Journal	Cellular Signalling
Volume	22
Issue number	11
DOIs	https://doi.org/10.1016/j.cellsig.2010.07.008
State	Published - Nov 2010

Keywords

AMP-activated protein kinase
Apoptosis
Epithelial-to-mesenchymal transition
TGF-beta

ASJC Scopus subject areas

Cell Biology

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10.1016/j.cellsig.2010.07.008

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

abstract = "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.",

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AU - Pan, Xinchao

AU - Song, Jianguo

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N2 - 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.

AB - 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.

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KW - Apoptosis

KW - Epithelial-to-mesenchymal transition

KW - TGF-beta

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

Abstract

Keywords

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