Selenium Suppressed Hydrogen Peroxide-Induced Vascular Smooth Muscle Cells Calcification Through Inhibiting Oxidative Stress and ERK Activation
Selenium Suppressed Hydrogen Peroxide-Induced Vascular Smooth Muscle Cells Calcification Through Inhibiting Oxidative Stress and ERK Activation
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DOI：
10.1002/jcb.22887
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发表时间：
2010-12-15
影响因子：
4
通讯作者：
Huang, Kaixun
中科院分区：
文献类型：
--
作者：
Liu, Hongmei;Lu, Qian;Huang, Kaixun
动脉粥样硬化常与血管钙化有关。越来越多的证据表明，人体必需的微量元素硒可以预防动脉粥样硬化，但硒在血管钙化中的作用尚不清楚。在这项研究中，我们评估了亚硒酸钠（Na 2SeO 3）对H2 O2增强的血管平滑肌细胞（VSMCs）钙化的影响，并检查了细胞外信号调节激酶（ERK）信号通路的参与。过氧化氢通过诱导VSMC的成骨细胞分化来增强血管钙化，如通过上调I型胶原、骨钙素和Runx 2（成骨细胞分化的关键转录因子）的mRNA表达、增加碱性磷酸酶活性和钙沉积所示。用亚硒酸盐（0.1-1 μ M）预处理细胞24小时可抑制H2 O2的这些作用。H2 O2可激活ERK 1/2的磷酸化，MEK抑制剂PD 98059抑制H2 O2激活的ERK信号通路可阻断H2 O2对VSMCs成骨分化的影响。此外，过氧化氢诱导氧化应激钙化VSMCs，细胞内活性氧的产生和丙二醛水平的增加，和总蛋白巯基含量和抗氧化硒谷胱甘肽过氧化物酶的活性的降低证明。亚硒酸盐预处理也减弱H2 O2诱导的氧化应激和ERK激活。这些结果表明，亚硒酸盐抑制H2 O2促进成骨细胞分化和钙化的VSMCs通过抑制氧化应激和ERK激活，表明硒在血管钙化的潜在预防作用。J.细胞。111：1556-1564，2010. (C)2010 Wiley-Liss，Inc.
Atherosclerosis is frequently associated with vascular calcification. Increasing evidences underline that the essential micronutrient selenium may prevent atherosclerosis, but the role of selenium in vascular calcification remains unknown. In this study, we assessed the effect of sodium selenite (Na2SeO3) on H2O2-enhanced vascular smooth muscle cells (VSMCs) calcification and examined the involvement of extracellular signal-regulated kinase (ERK) signaling pathway. Hydrogen peroxide enhanced vascular calcification by inducing osteoblastic differentiation of VSMCs, as showed by up-regulating the mRNA expression of type I collagen, osteocalcin, and Runx2, a key transcription factor for osteoblastic differentiation, increasing alkaline phosphatase activity, and calcium deposition. These effects of H202 were suppressed by pretreatment of the cells with selenite (0.1-1 mu M) for 24h. In addition, H2O2 activated the phosphorylation of ERK1/2 and inhibition of H2O2-activated ERK signaling by MEK inhibitor PD98059 blocked the effect of H2O2 on osteoblastic differentiation of VSMCs. Furthermore, H2O2 induced oxidative stress in calcifying VSMCs, as evidenced by the increase of intracellular reactive oxygen species production and malondialdehyde level, and the decrease of total protein thiols content and the activity of antioxidant selenoenzyme glutathione peroxidases. Selenite pretreatment also attenuated H2O2-induced oxidative stress and ERK activation. These results suggested that selenite suppressed H2O2-enhanced osteoblastic differentiation and calcification of VSMCs through inhibiting oxidative stress and ERK activation, indicating a potential preventive role for selenium in vascular calcification. J. Cell. Biochem. 111: 1556-1564, 2010. (C) 2010 Wiley-Liss, Inc.