AMP-Activated Protein Kinase Inhibits Homocysteine-Induced Dysfunction and Apoptosis in Endothelial Progenitor Cells
AMP-Activated Protein Kinase Inhibits Homocysteine-Induced Dysfunction and Apoptosis in Endothelial Progenitor Cells
复制标题
AMP 激活蛋白激酶抑制同型半胱氨酸诱导的内皮祖细胞功能障碍和凋亡
DOI：
10.1007/s10557-010-6277-1
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发表时间：
2011-02-01
影响因子：
3.4
通讯作者：
Lu, Guoping
中科院分区：
文献类型：
--
作者：
Jia, Fang;Wu, Chunfang;Lu, Guoping
Homocysteine (Hcy) has been shown to induce oxidative stress and apoptosis of endothelial progenitor cells (EPCs). AMP-activated protein kinase (AMPK) has been reported to have protective effects on endothelial function. However, effects of AMPK activation on Hcy-induced EPCs injury remain to be determined. In this study, we examined the effect of AMPK phosphorylation on Hcy-induced NO bioavailability impairment and NADPH oxidase 4 (Nox4) derived reactive oxygen species (ROS) accumulation in EPCs.EPCs were pre-treated with various concentrations of 5-amino-4-imidazolecarboxamide riboside-l-beta-D-ribofuranoside (AICAR), a pharmacological agonist of AMPK, and then incubated with Hcy for 24 h. Furthermore, we challenged EPCs with Hcy in the presence or absence of atorvastatin and AMPK-DN which expressed a dominant-negative mutant of AMPK. Migration, proliferation and apoptosis were assayed to evaluate EPCs function. NO production, expression of endothelial nitric oxide synthase (eNOS), intracellular ROS levels and Nox4 activation were determined to explore the potential mechanisms of Hcy-induced EPCs dysfunction.We observed that AICAR attenuated the inhibition effects of Hcy on EPCs migration and proliferation. The apoptosis rates of EPCs were down-regulated by AICAR compared with the group treated with Hcy only [(0.25 mmol/L AICAR: 10.48 +/- 1.6%; 0.5 mmol/L AICAR: 8.70 +/- 1.0%; 1 mmol/L AICAR: 5.83 +/- 1.3%) vs. (500 mu mol/L Hcy only: 12.60 +/- 1.9%)]. We also found that NO production and eNOS expression were up-regulated by AICAR compared with the group treated with Hcy only, while ROS accumulation and Nox4 activation were inhibited. Furthermore, atorvastatin suppressed Hcy-induced dysfunction of EPCs, increased NO production and eNOS expression, and down-regulated ROS accumulation and Nox4 activation. And these effects of atorvastatin could be blunted by AMPK-DN.AMPK activation inhibits eNOS down-regulation and Nox4-derived ROS accumulation induced by Hcy in EPCs, and may contribute to the protective effects of atorvastatin on endothelial function.
