Rapid activation of protein kinase B/Akt has a key role in antiapoptotic signaling during liver regeneration
Rapid activation of protein kinase B/Akt has a key role in antiapoptotic signaling during liver regeneration
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DOI：
10.1006/bbrc.2000.4044
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发表时间：
2000-12-29
影响因子：
3.1
通讯作者：
Gao, B
中科院分区：
文献类型：
--
作者：
Hong, F;Nguyen, VA;Gao, B
肝再生受多种生长因子、激素和细胞因子诱导的多种信号通路控制。在这里，我们报告，蛋白激酶B（PKB）/Akt，一个关键的细胞存活信号通路的一部分，在部分肝切除术（PHX）后显着激活。PKB/Akt的下游靶点抗凋亡蛋白Bad也被磷酸化。该级联反应可被原代肝细胞中的各种因子激活，其中胰岛素和α（1）-肾上腺素能激动剂苯肾上腺素（PE）的激活作用最强，其次是IL-6、表皮生长因子（EGF）和肝细胞生长因子（HGF）。用特异性PI 3激酶抑制剂LY 294002预处理细胞可阻断胰岛素或PE对PKB/ Akt的激活，表明PKB/Akt的激活是由PI 3激酶依赖性机制介导的。在体内给予PE、胰岛素、IL-6、HGF或EGF对小鼠肝脏中的PKB/Akt有显著刺激作用，其中胰岛素和PE诱导的刺激作用最强。此外，HGF和胰岛素能够减弱转化生长因子β诱导的肝细胞凋亡，并且这些作用被LY 294002拮抗。总之，这些发现表明，PKB/Akt的快速激活是一个关键的抗凋亡信号通路参与肝再生。(C)北京大学出版社.
Liver regeneration is controlled by multiple signaling pathways induced by a variety of growth factors, hormones, and cytokines. Here we report that protein kinase B (PKB)/Akt, part of a key cell survival signaling pathway, is markedly activated after partial hepatectomy (PHX). The antiapoptotic protein Bad, a downstream target of PKB/Akt, is also phosphorylated, This cascade can be activated by various factors in primary hepatocytes, with the strongest activation by insulin and the alpha (1)-adrenergic agonist phenylephrine (PE), followed by IL-6, epidermal growth factor (EGF), and hepatocyte growth factor (HGF). Pretreatment of cells with the specific PI3 kinase inhibitor LY294002 abolished insulin- or PE-activation of PKB/ Akt, suggesting that activation of PKB/Akt is mediated by a PI3 kinase-dependent mechanism. In vivo administration of PE, insulin, IL-6, HGF, or EGF to mice markedly stimulated PKB/Akt in the liver, with the strongest stimulation induced by insulin and PE. Moreover, HGF and insulin were able to attenuate transforming growth factor beta -induced apoptosis in hepatic cells, and these effects were antagonized by LY294002. Taken together, these Findings suggest that rapid activation of PKB/Akt is a key antiapoptotic signaling pathway involved in liver regeneration. (C) 2000 Academic Press.