Rottlerin activates AMPK possibly through LKB1 in vascular cells and tissues
Rottlerin activates AMPK possibly through LKB1 in vascular cells and tissues
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DOI：
10.1016/j.bbrc.2008.09.007
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发表时间：
2008-11-14
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
--
作者：
Kojima, Kanou;Motoshima, Hiroyuki;Araki, Eiichi
AMP激活的蛋白激酶（AMPK）是一种参与多种细胞信号转导途径的细胞能量传感器，已成为血管疾病的一个有吸引力的治疗靶点。目前尚不清楚蛋白激酶C δ抑制剂rottlerin是否激活血管细胞和组织中的AMPK。在本研究中，我们研究了rottlerin对AMPK在血管平滑肌细胞（VSMCs）和离体兔主动脉的影响。在VSMCs和兔主动脉中，Rottlerin降低细胞ATP并激活AMPK;然而，通过三种不同方法抑制PKC δ并不激活AMPK。VSMCs和兔主动脉表达上游AMPK激酶LKB 1蛋白，并且通过显性负性LKB 1的过表达降低VSMCs中rottlerin诱导的AMPK活化，表明LKB 1参与了rottlerin刺激的AMPK的上游调节。这些数据首次表明，LKB 1介导了血管细胞和组织中罗特勒素诱导的AMPK活化。(C)2008年爱思唯尔公司All rights reserved.
AMP-activated protein kinase (AMPK) is a cellular energy sensor involved in multiple cell signaling pathways that has become an attractive therapeutic target for vascular diseases. It is not clear whether rottlerin, an inhibitor of protein kinase C delta, activates AMPK in vascular cells and tissues. In the present study, we have examined the effect of rottlerin on AMPK in vascular smooth muscle cells (VSMCs) and isolated rabbit aorta. Rottlerin reduced cellular ATP and activated AMPK in VSMCs and rabbit aorta; however, inhibition of PKC delta by three different methods did not activate AMPK. Both VSMCs and rabbit aorta expressed the upstream AMPK kinase LKB1 protein, and rottlerin-induced AMPK activation was decreased in VSMCs by overexpression of dominant-negative LKB1, suggesting that LKB1 is involved in the upstream regulation of AMPK stimulated by rottlerin. These data suggest for the first time that LKB1 mediates rottlerin-induced activation of AMPK in vascular cells and tissues. (C) 2008 Elsevier Inc. All rights reserved.