The effect of AMP-activated protein kinase and its activator AICAR on the metabolism of human umbilical vein endothelial cells
The effect of AMP-activated protein kinase and its activator AICAR on the metabolism of human umbilical vein endothelial cells
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DOI：
10.1006/bbrc.1999.1635
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发表时间：
1999-11-11
影响因子：
3.1
通讯作者：
Ido, Y
中科院分区：
文献类型：
--
作者：
Dagher, Z;Ruderman, N;Ido, Y
在已研究的几种非血管组织中，AMP 激活蛋白激酶 (AMPK) 似乎可以调节细胞对缺血等应激的反应。在肝脏和肌肉中，它磷酸化并抑制乙酰辅酶A羧化酶（ACC），导致脂肪酸氧化增加；在肌肉中，它的激活与葡萄糖转运的增加有关。在这里，我们报告了人脐静脉内皮细胞 (HUVEC) 中同时存在 AMPK 和 ACC。 HUVEC 与 2 mM AICAR（一种 AMPK 激活剂）一起孵育，导致 AMPK 激活 5 倍，同时 ACC 活性降低 70%，脂肪酸氧化增加 2 倍。令人惊讶的是，HUVEC 中主要的能量产生途径葡萄糖摄取和糖酵解减少了 40-60%。尽管如此，细胞 ATP 水平仍增加了 35%。从而激活AMPK。 AICAR 的治疗与内皮细胞能量平衡的重大改变有关。这些改变是否在缺血或其他应激期间保护内皮仍有待确定。 (C) 1999 年学术出版社。
In several non-vascular tissues in which it has been studied, AMP-activated protein kinase (AMPK) appears to modulate the cellular response to stresses such as ischemia. In liver and muscle, it phosphorylates and inhibits acetyl CoA carboxylase (ACC), leading to an increase in fatty acid oxidation; and in muscle, its activation is associated with an increase in glucose transport. Here we report the presence of both AMPK and ACC in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with 2 mM AICAR, an AMPK activator, caused a 5-fold activation of AMPK, which was accompanied by a 70% decrease in ACC activity and a 2-fold increase in fatty acid oxidation. Surprisingly, glucose uptake and glycolysis, the dominant energy-producing pathway in HUVEC, were diminished by 40-60%. Despite this, cellular ATP levels were increased by 35%. Thus activation of AMPK. by AICAR is associated with major alterations in endothelial cell energy balance. Whether these alterations protect the endothelium during ischemia or other stresses remains to be determined. (C) 1999 Academic Press.