Influence of various fatty acids on the activity of protein phosphatase type 2C and apoptosis of endothelial cells and macrophages
Influence of various fatty acids on the activity of protein phosphatase type 2C and apoptosis of endothelial cells and macrophages
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DOI：
10.1016/j.ejps.2008.08.007
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发表时间：
2008-12-18
影响因子：
4.6
通讯作者：
Klumpp, Susanne
中科院分区：
文献类型：
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作者：
Krieglstein, Josef;Hufnagel, Birgit;Klumpp, Susanne
在以前的工作中，我们已经证明了蛋白磷酸酶2C(PP2C)a和p可以被单不饱和脂肪酸(MUFAs)激活，导致培养的内皮细胞凋亡。在这篇论文中，我们可以证明饱和脂肪酸(SFA)不能激活PP2C，也不能引起内皮细胞和巨噬细胞的凋亡。然而，长链SFA(~gt；16个C原子)既能抑制油酸引起的人脐静脉内皮细胞(HUVECs)和巨噬细胞的PP2C活化，又能抑制其诱导的细胞凋亡。有趣的是，二十二碳六烯酸(DHA)在高浓度(200-400mU M)时可引起血管内皮细胞的凋亡，但在低浓度时(1-10mU M)可抑制HUVECs的凋亡损伤。相反，油酸即使在低浓度(1-25mM)时也不能保护HUVECs免受损伤。据推测，血液中MUFAs水平的失衡和长期升高有可能导致动脉粥样硬化。此外，由MUFAs激活的PP2C有望成为预防或治疗动脉粥样硬化药物的新靶点。(C)2008爱思唯尔B.V.保留所有权利
In previous work we have demonstrated that protein phosphatase type 2C (PP2C) a and p can be activated by mono-unsaturated fatty acids (MUFAs) leading to apoptosis of cultured endothelial cells. in the present paper we could show that saturated fatty acids (SFAs) did not activate PP2C and did not cause apoptosis both in endothelial cells and macrophages. However, long-chain SFAs (>16 C-atoms) were capable of inhibiting both, activation of PP2C as well as apoptosis of human umbilical vein endothelial cells (HUVECs) and macrophages caused by oleic acid. Interestingly, docosahexaenoic acid (DHA) known to protect arterial vessels against the progression of atherosclerosis caused apoptosis of HUVECs at high concentrations (200-400 mu M) but inhibited the apoptotic damage of HUVECs at a low, physiologically relevant concentration range (1-10 mu M). In contrast, oleic acid did not protect HUVECs against damage even at low concentrations (1-25 mu M). It is supposed that an unbalanced and chronically increased level of MUFAs in blood has an atherosclerotic potential. Furthermore, PP2C activated by MUFAs appears as a new target for drugs to prevent or treat atherosclerosis. (C) 2008 Elsevier B.V. All rights reserved