Expression of the nuclear factor-κB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells:: Possible links to hypertension, atherogenesis, and stroke
Expression of the nuclear factor-κB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells:: Possible links to hypertension, atherogenesis, and stroke
复制标题
DOI：
10.1016/s0895-7061(03)00987-7
复制
发表时间：
2003-09-01
影响因子：
3.2
通讯作者：
Altura, BT
中科院分区：
文献类型：
--
作者：
Altura, BM;Kostellow, AB;Altura, BT
原癌基因（c-fos、c-jun）和核因子-κ B（NF-κ B）表达以及DNA合成在主动脉和脑血管平滑肌细胞（VSMCs）中受到细胞外镁离子（[Mg 2 +]（o））减少的上调。这些转录因子的上调与[Mg 2 +]（o）成反比，并且发生在高血压、缺血性心脏病和中风患者血清的病理生理范围内。用硝苯地平或蛋白激酶C（PKC）抑制剂去除细胞外Ca 2+（[Ca 2 +]（o）]可阻止原癌基因和VSMC DNA合成的上调。这些数据表明，[Mg ~（2+）]（o）可能是VSMCs中原癌基因和NF-κ B表达的重要的、迄今为止被忽视的天然调节剂，并且Ca ~（2+）和PKC可能在由[Mg ~（2+）]（o）减少诱导的VSMCs中c-fos和c-jun的诱导中起关键作用。这些结果表明低血清Mg 2+在高血压、动脉粥样硬化、血管疾病和中风的潜在发展中的作用。
Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magmesium ions ([Mg2+](o)). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+](o) and occurred over the pathophysiologic range of serum found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+](o)] use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+](o) may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+](o). These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.