ERK2 activation by homocysteine in vascular smooth muscle cells
ERK2 activation by homocysteine in vascular smooth muscle cells
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DOI：
10.1006/bbrc.1998.9535
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发表时间：
1998-10-29
影响因子：
3.1
通讯作者：
Monaghan, DT
中科院分区：
文献类型：
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作者：
Brown, JC;Rosenquist, TH;Monaghan, DT
同型半胱氨酸水平异常高是动脉粥样硬化的独立危险因素，可能是动脉粥样硬化形成的关键因素。由于同型半胱氨酸(Hcys)可以促进血管平滑肌细胞(VSMCs)的增殖和基因转录因子c-fos的诱导，这种作用可以通过MAP激酶介导，我们推测Hcys激活了MAP依赖的信号转导通路。在这项研究中，我们发现同型半胱氨酸瞬时激活培养的鸡胚胎血管平滑肌细胞中的MAPK(ERK2亚型)。同型半胱氨酸对ERK2的激活呈剂量依赖性，EC50约为500 nM，并可被MAP/ERK激酶(MEK)抑制剂PD98059阻断。VSMC胚胎血统是同型半胱氨酸敏感性的另一个决定因素。这些发现表明，同型半胱氨酸激活了MAP激酶信号转导通路，从而支持了同型半胱氨酸可能通过刺激促生长信号转导通路而促进动脉粥样硬化的假说。(C)1998年学术出版社。
Homocysteine at abnormally high levels is an independent risk factor for atherosclerosis and may be a key factor in atherogenesis. Since homocysteine (Hcys) has been shown to promote cell proliferation and induction of the gene transcription factor c-fos in vascular smooth muscle cells (VSMCs), effects which can be mediated by MAP kinase, we hypothesized that homocysteine activates a MAP kinase-dependent signal transduction pathway. In this study, we find that homocysteine transiently activates MAP kinase (ERK2 isoform) in cultured VSMCs from chick embryos. Homocysteine activation of ERK2 is dose-dependent with an EC50 of approximately 500 nM and blocked by the MAP/Erk kinase (MEK) inhibitor PD98059. VSMC embryonic lineage is another determinant of homocysteine sensitivity. These findings demonstrate that homocysteine activates the MAP kinase signal transduction pathway and thus support the hypothesis that homocysteine may promote atherosclerosis by stimulation of growth promoting signal transduction pathways. (C) 1998 Academic Press.