Leclerc I, Kahn A, Doiron B
Institut Cochin de Génétique Moléculaire, INSERM, Unité 129, Paris, France.
FEBS Lett. 1998 Jul 17;431(2):180-4. doi: 10.1016/s0014-5793(98)00745-5.
5-Amino-4-imidazolecarboxamide riboside (AICAR) is known to stimulate rat liver 5'-AMP-activated protein kinase (AMPK). AMPK is the mammalian homologue of Snf1p in yeast, involved in derepression of glucose-repressed genes. We used AICAR to test if AMPK could also play a role in the regulation of glucose-dependent genes in mammalian cells. At a concentration which induces phosphorylation-dependent inactivation of HMG-CoA reductase, AICAR blocked glucose activation of three glucose responsive genes, namely L-type pyruvate kinase (L-PK), Spot 14 and fatty acid synthase genes in primary cultured hepatocytes, but was without any action on glucose phosphorylation to glucose 6-phosphate and on expression of PEPCK, albumin and beta-actin genes. AICAR was also found to inhibit activation of the L-PK gene promoter by glucose in transiently transfected hepatoma cells. Therefore our results suggest that AMPK is probably involved in the glucose signal pathway regulating gene expression in the liver.
已知5-氨基-4-咪唑甲酰胺核苷（AICAR）可刺激大鼠肝脏5'-AMP激活的蛋白激酶（AMPK）。AMPK是酵母中Snf1p的哺乳动物同源物，参与解除葡萄糖抑制基因的阻遏。我们使用AICAR来测试AMPK是否也能在哺乳动物细胞中调控葡萄糖依赖性基因。在诱导HMG-CoA还原酶磷酸化依赖性失活的浓度下，AICAR阻断了原代培养肝细胞中三个葡萄糖反应性基因（即L型丙酮酸激酶（L-PK）、Spot 14和脂肪酸合酶基因）的葡萄糖激活，但对葡萄糖磷酸化为6-磷酸葡萄糖以及磷酸烯醇式丙酮酸羧激酶（PEPCK）、白蛋白和β-肌动蛋白基因的表达没有任何作用。还发现AICAR可抑制瞬时转染的肝癌细胞中葡萄糖对L-PK基因启动子的激活。因此，我们的结果表明，AMPK可能参与了肝脏中调节基因表达的葡萄糖信号通路。
