Beyond AICA riboside: in search of new specific AMP-activated protein kinase activators.
Beyond AICA riboside: in search of new specific AMP-activated protein kinase activators.
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DOI：
10.1002/iub.135
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发表时间：
2009-01
期刊：
影响因子：
4.6
通讯作者：
Hue, Louis
中科院分区：
文献类型：
--
作者：
Guigas, Bruno;Sakamoto, Kei;Taleux, Nellie;Reyna, Sara M.;Musi, Nicolas;Viollet, Benoit;Hue, Louis
关键词：
5-氨基咪唑-4-carboxamide-1-β-d-核糖呋喃苷（AICA核糖苷）已广泛用于体外和体内激活amp活化的蛋白激酶（AMPK）， AMPK是一种参与细胞和全身能量稳态的代谢传感器。然而，最近有研究强调，AICA核苷也具有不依赖AMPK的作用，主要作用于amp调节的酶和线粒体氧化磷酸化（OXPHOS），从而得出结论，需要降低脱靶效应的新化合物才能特异性激活AMPK。在这里，我们回顾了最近新发现的AMPK激活剂，特别是a -769662，一种来自噻唑吡酮家族的非核苷化合物。我们还报道了A-769662能够激活AMPK并刺激L6细胞和源自人类卫星细胞的原代肌管的葡萄糖摄取。此外，A-769662在原代培养的大鼠肝细胞中增加AMPK活性及其主要下游靶点的磷酸化，但与AICA核苷相比，不影响线粒体OXPHOS，也不改变细胞AMP:ATP比率。我们认为A-769662可能是一种新的有前景的化学制剂，可以激活AMPK，并且AMPK非依赖性副作用有限。
5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to activate the AMP-activated protein kinase (AMPK), a metabolic sensor involved in both cellular and whole body energy homeostasis. However, it has been recently highlighted that AICA riboside also exerts AMPK-independent effects, mainly on AMP-regulated enzymes and mitochondrial oxidative phosphorylation (OXPHOS), leading to the conclusion that new compounds with reduced off target effects are needed to specifically activate AMPK. Here, we review recent findings on newly discovered AMPK activators, notably on A-769662, a nonnucleoside compound from the thienopyridone family. We also report that A-769662 is able to activate AMPK and stimulate glucose uptake in both L6 cells and primary myotubes derived from human satellite cells. In addition, A-769662 increases AMPK activity and phosphorylation of its main downstream targets in primary cultured rat hepatocytes but, by contrast with AICA riboside, does neither affect mitochondrial OXPHOS nor change cellular AMP:ATP ratio. We conclude that A-769662 could be one of the new promising chemical agents to activate AMPK with limited AMPK-independent side effects.
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
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