Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C
Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C
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DOI：
10.1038/emm.2004.15
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发表时间：
2004-04-30
影响因子：
12.8
通讯作者：
Min, DS
中科院分区：
文献类型：
--
作者：
Kim, J;Min, G;Min, DS
氧化应激与血管疾病的介导有关。在钒酸盐存在下，过氧化氢诱导大鼠血管平滑肌细胞（VSMCs）中PLD 1、蛋白激酶C-α（PKC-α）和其他未鉴定蛋白的酪氨酸磷酸化。有趣的是，发现PLD 1与VSMC中的PKC-α组成性相关。H2 O2和钒酸盐刺激的细胞表现出浓度依赖性的酪氨酸磷酸化的蛋白质在PLD 1免疫沉淀和激活PLD。预处理的细胞与蛋白酪氨酸激酶抑制剂，染料木素导致剂量依赖性抑制H2 O2诱导的PLD激活。PKC抑制剂和PKC下调可阻断H2 O2诱导的PLD激活。氧化应激（H2 O2）刺激的细胞引起细胞迁移增加。用酪氨酸激酶抑制剂、PKC抑制剂和1-丁醇预处理细胞，但不能用3-丁醇预处理细胞，可以防止这种作用。总之，这些结果表明，PLD可能参与氧化应激诱导的VSMCs迁移，可能通过酪氨酸磷酸化和PKC激活。
Oxidative stress has been implicated in mediation of vascular disorders. In the presence of vanadate, H2O2 induced tyrosine phosphorylation of PLD1, protein kinase C-alpha (PKC-alpha), and other unidentified proteins in rat vascular smooth muscle cells (VSMCs). Interestingly, PLD1 was found to be constitutively associated with PKC-alpha in VSMCs. Stimulation of the cells by H2O2 and vanadate showed a concentration-dependent tyrosine phosphorylation of the proteins in PLD1 immunoprecipitates and activation of PLD. Pretreatment of the cells with the protein tyrosine kinase inhibitor, genistein resulted in a dose-dependent inhibition of H2O2-induced PLD activation. PKC inhibitor and down-regulation of PKC abolished H2O2-stimulated PLD activation. The cells stimulated by oxidative stress (H2O2) caused increased cell migration. This effect was prevented by the pretreatment of cells with tyrosine kinase inhibitors, PKC inhibitors, and 1-butanol, but not 3-butanol. Taken together, these results suggest that PLD might be involved in oxidative stress-induced migration of VSMCs, possibly via tyrosine phosphorylation and PKC activation.