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

AMP-activated protein kinase is required for induction of apoptosis and epithelial-to-mesenchymal transition.
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AMP 激活的蛋白激酶是诱导细胞凋亡和上皮间质转化所必需的。

DOI:
10.1016/j.cellsig.2010.07.008
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发表时间:
2010-11
影响因子:
4.8
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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AMP激活的蛋白激酶(AMPK)是一种丝氨酸/苏氨酸蛋白激酶,参与细胞能量稳态的调节。对于它在其他细胞过程中的作用,人们知之甚少。我们观察到AMPK-α可被转化生长因子-β-1(TGFR-β-1)激活。选择性AMPK-α抑制剂C抑制AMPK可抑制转化生长因子-β-1诱导的肝细胞凋亡和肝细胞转分化。此外,显性-负性AMPK-α亚基的过表达也抑制了转化生长因子-β1诱导的细胞内皮细胞转化和细胞凋亡。此外,抑制AMPK可抑制转化生长因子-β1诱导的Smad3转录活性。本研究表明,AMPK能够调节Smad3的转录活性,在转化生长因子-β-1诱导的细胞凋亡和子宫内膜间质转化中起重要作用。
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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影响因子: --
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