AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2α in adipocytes
AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2α in adipocytes
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DOI：
10.1016/j.bbrc.2005.11.159
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发表时间：
2006-02-03
影响因子：
3.1
通讯作者：
Berry, EM
中科院分区：
文献类型：
--
作者：
Dagon, Y;Avraham, Y;Berry, EM
腺苷酸活化蛋白激酶（AMPK）是调节糖、脂代谢的代谢总开关。最近，AMPK已被牵连在脂肪组织含量的控制。然而，这一行动的性质是有争议的。我们检测了AMPK激活剂AICAR对F442 a脂肪细胞的作用。AMPK的激活诱导剂量依赖性凋亡细胞死亡，抑制脂解，并下调关键的脂肪形成基因，如过氧化物酶体增殖物激活受体（PPAR γ）和CCAAT/增强子结合蛋白α（C/EBP α）。我们已经鉴定了真核起始因子-2（eIF 2 α）的α-亚基作为靶基因，其在AICAR处理后被磷酸化。这种磷酸化是下调蛋白质合成的最佳表征机制之一。2-氨基嘌呤（2-AP），eIF 2 α激酶的抑制剂，可以克服AICAR的凋亡作用，消除减少的PPAR γ和C/EBP α和AMPK的脂解特性。因此，AMPK可以通过eIF 2 α依赖性翻译关闭减少脂肪细胞数量来减少肥胖。(c)2005年爱思唯尔公司All rights reserved.
AMP-activated protein kinase (AMPK) is a metabolic master switch regulating glucose and lipid metabolism. Recently, AMPK has been implicated in the control of adipose tissue content. Yet, the nature of this action is controversial. We examined the effect on F442a adipocytes of the AMPK activator-AICAR. Activation of AMPK induced dose-dependent apoptotic cell death, inhibition of lipolysis, and downregulatation key adipogenic genes, such as peroxisome proliferator-activated receptor (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP alpha). We have identified the a-subunit of the eukaryotic initiation factor-2 (eIF2 alpha) as a target gene which is phosphorylated following AICAR treatment. Such phosphorylation is one of the best-characterized mechanisms for downregulating protein synthesis. 2-Aminopurine (2-AP), an inhibitor of eIF2 alpha kinases, could overcome the apoptotic effect of AICAR, abolishing the reduction of PPAR gamma and C/EBP alpha and the lipolytic properties of AMPK. Thus, AMPK may diminish adiposity via reduction of fat cell number through eIF2 alpha-dependent translation shutdown. (c) 2005 Elsevier Inc. All rights reserved.