Regulation of VEGF-induced endothelial cell PAF synthesis:: role of p42/44 MAPK, p38 MAPK and PI3K pathways
Regulation of VEGF-induced endothelial cell PAF synthesis:: role of p42/44 MAPK, p38 MAPK and PI3K pathways
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DOI：
10.1038/sj.bjp.0704367
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发表时间：
2001-11-01
影响因子：
7.3
通讯作者：
Sirois, MG
中科院分区：
文献类型：
--
作者：
Bernatchez, PN;Allen, BG;Sirois, MG
1 血管内皮生长因子 (VEGF) 是一种有效的血管生成和炎症介质。我们最近表明，后一种作用需要激活 Flk-1 受体和随后的内皮细胞（EC PAF 合成）。然而，在 VEGF 刺激 Flk-1 后调节 EC PAF 合成的细胞内事件仍有待阐明。2 使用特异性抑制剂和蛋白质印迹分析，我们在此报告，在牛主动脉内皮细胞 (BAEC) 中，VEGF 通过 Flk-1 受体、磷脂酶 C γ 的级联激活诱导 PAF 的合成(PLC gamma)、蛋白激酶 C (PKC) 和 p42/44 丝裂原激活蛋白激酶 (MAPK)。3 此外，我们证明 VEGF 介导的 PAF 合成需要 p38 MAPK 的激活，可能是通过指导 lyso-PAF 转化为 PAF。4 有趣的是，我们观察到 VEGF 还促进了磷脂酰肌醇 3-磷酸激酶 (PI3K) 途径的激活，并且其阻断增强了 PAF因此，PI3K 通路似乎充当 EC PAF 合成的负调节因子。5 总而言之，这些结果可以更好地了解 VEGF 刺激 EC 时激活的细胞内事件，并为 VEGF 诱导 PAF 合成的机制提供新的线索。
1 Vascular endothelial growth factor (VEGF) is a potent angiogenic and inflammatory mediator. We have recently shown that this latter effect requires the activation of Flk-1 receptor and subsequent endothelial cell (EC PAF synthesis. However, the intracellular events that regulate EC PAF synthesis upon Flk-1 stimulation by VEGF remain to be, elucidated.2 Using specific inhibitors and Western blot analysis, we herein report that in bovine aortic endothelial cells (BAEC), VEGF induces the synthesis of PAF through the cascade activation of Flk-1 receptor, phospholipase C gamma (PLC gamma), protein kinase C (PKC) and p42/44 mitogen-activated protein kinases (MAPK).3 Moreover, we demonstrate that VEGF-mediated PAF synthesis requires the activation of p38 MAPK, likely by directing the conversion of lyso-PAF to PAF.4 Interestingly, we observed that VEGF also promoted the activation of the phosphatidyl inositol-3-phosphate kinase (PI3K) pathway, and that its blockade potentiated PAF synthesis following a VEGF treatment. Consequently, it appears that the PI3K pathway acts as a negative regulator of EC PAF synthesis.5 Taken together, these results allow a better understanding of the intracellular events activated upon EC stimulation by VEGF, and shed a new light on the mechanisms by which VEGF induces PAF synthesis.