Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating amp-activated protein kinase
Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating amp-activated protein kinase
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阿托伐他汀通过激活 AMP 激活的蛋白激酶来防止间充质干细胞缺氧和无血清损伤。
DOI：
10.1016/j.ijcard.2010.08.047
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发表时间：
2011-12-15
影响因子：
3.5
通讯作者：
Xu, Zhimin
中科院分区：
文献类型：
--
作者：
Dong, Qiuting;Yang, Yuejin;Xu, Zhimin
背景资料：骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是治疗心肌梗死的最佳候选细胞，但移植后细胞存活率较低，影响了其治疗优势。近年来研究表明，他汀类药物可通过增加内皮型一氧化氮合酶（eNOS）活性，提高缺氧无血清（H/SF）条件下细胞的存活率，从而对心血管系统产生多效性作用。腺苷酸活化蛋白激酶（AMPK）是维持各种组织能量产生和代谢平衡的重要组成部分，是调节细胞程序性死亡的主导因子。因此，我们假设，阿托伐他汀可以保护骨髓间充质干细胞从H/SF通过AMPK-eNOS pathway.Methods和结果：染色与Annexin V/propidine iodine（PI），我们发现阿托伐他汀（0.001 μ M-10 μ M）减少细胞凋亡的猪骨髓来源的骨髓间充质干细胞培养在H/SF条件下，然而，这种效果被阻断化合物C，AMPK的抑制剂。这种趋势与Western印迹分析的促凋亡蛋白bax蛋白相似;而抗凋亡蛋白bcl-2蛋白在阿托伐他汀处理的细胞中增加。同时，阿托伐他汀处理的MSC增加AMPK和eNOS的磷酸化。结论：阿托伐他汀可激活AMPK，AMPK的磷酸化导致eNOS的激活，为他汀类药物对心血管系统的多重作用提供了新的解释。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Background: Mesenchymal stem cells (MSCs) are the optimal candidate of treating myocardial infarction; however, the lower survival ratio of implanted cell discourages the advantages of this treatment. Recent studies have displayed statins, which exert pleiotropic effects on the cardiovascular system partially through the increase in endothelial nitric oxide synthase (eNOS) activity, could increase the livability of cells under hypoxia and serum-free (H/SF) conditions. AMP-activated protein kinase (AMPK) is the essential part in keeping the balance of energy production and metabolism in various tissues, which is the dominant factor modulating the programmed cell death. Therefore, we hypothesized that atorvastatin could protect MSCs from H/SF injury through AMPK-eNOS pathway.Methods and results: Stained with Annexin V/propidine iodine (PI), we found atorvastatin (0.001 mu M-10 mu M) reduced apoptosis of porcine bone marrow-derived MSCs cultured in H/SF condition; however, this effect was obstructed by compound C, an inhibitor of AMPK. This trend was similar as what bax protein, a pro-apoptosis protein, showed analyzed by Western blotting; whereas the bcl-2 protein, an anti-apoptosis protein, increased in atorvastatin treated cells. Meanwhile, MSCs treated with atorvastatin increased phosphorylation of AMPK and eNOS. The uptrend was partially inhibited by compound C.Conclusions: Atorvastatin can activate AMPK and the phosphorylation of AMPK results in eNOS activated, which provides a novel explanation for the multi-effect of statins on cardiovascular system. (C) 2010 Elsevier Ireland Ltd. All rights reserved.