Shimizu H, Takayama H, Lee J D, Satake K, Taniguchi T, Yamamura H, Nakamura T
First Department of Internal Medicine, Fukui Medical School, Japan.
Thromb Haemost. 1994 Dec;72(6):973-8.
The ability of vanadate, an inhibitor of protein-tyrosine phosphatases, to affect the production of prostacyclin (PGI2) and endothelin-1 (ET-1) and protein-tyrosine phosphorylation in human umbilical vein endothelial cells (HUVEC) was studied. The addition of vanadate to monolayers of cultured HUVEC caused a sustained release of PGI2 from HUVEC in a time- and dose-dependent manner. When aspirin-treated HUVEC, which have lost the ability to increase PGI2 production in response to arachidonate, were incubated with vanadate, the cells recovered their ability to increase PGI2 production in response to arachidonate. This recovery of inducible PGI2 production in aspirin-treated HUVEC was completely inhibited either by cycloheximide, a protein synthesis inhibitor, or by actinomycin D, an RNA synthesis inhibitor. In contrast, the same concentration of vanadate suppressed the basal release of ET-1 from HUVEC. Vanadate also caused an increase in protein-tyrosine phosphorylation in HUVEC. These data indicate that vanadate induces opposite effects on PGI2 and ET-1 production with a concomitant increase in protein-tyrosine phosphorylation in HUVEC.
研究了蛋白酪氨酸磷酸酶抑制剂钒酸盐对人脐静脉内皮细胞（HUVEC）中前列环素（PGI2）和内皮素 -1（ET -1）产生以及蛋白酪氨酸磷酸化的影响。向培养的HUVEC单层中添加钒酸盐会导致HUVEC以时间和剂量依赖性方式持续释放PGI2。当用阿司匹林处理过的HUVEC（已失去响应花生四烯酸增加PGI2产生的能力）与钒酸盐一起孵育时，细胞恢复了响应花生四烯酸增加PGI2产生的能力。阿司匹林处理的HUVEC中诱导性PGI2产生的这种恢复被蛋白质合成抑制剂环己酰亚胺或RNA合成抑制剂放线菌素D完全抑制。相反，相同浓度的钒酸盐抑制了HUVEC中ET -1的基础释放。钒酸盐还导致HUVEC中蛋白酪氨酸磷酸化增加。这些数据表明，钒酸盐对PGI2和ET -1的产生诱导相反的作用，同时伴随着HUVEC中蛋白酪氨酸磷酸化的增加。
