A role of protein kinase C in the regulation of cytosolic phospholipase A2 in bradykinin-induced PGI2 synthesis by human vascular endothelial cells

被引：16

作者：

Higaki, T ^{[1
]}

Sawada, S ^{[1
]}

Kono, Y ^{[1
]}

Imamura, H ^{[1
]}

Tada, Y ^{[1
]}

Yamasaki, S ^{[1
]}

Toratani, A ^{[1
]}

Sato, T ^{[1
]}

Komatsu, S ^{[1
]}

Akamatsu, N ^{[1
]}

Tamagaki, T ^{[1
]}

Tsuda, Y ^{[1
]}

Tsuji, H ^{[1
]}

Nakagawa, M ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Med 2, Kyoto 602, Japan

来源：

MICROVASCULAR RESEARCH | 1999年 / 58卷 / 02期

关键词：

bradykinin; protein kinase C; cytosolic phospholipase A(2); prostacyclin; human vascular endothelial cells;

D O I：

10.1006/mvre.1999.2163

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The purpose of this study was to elucidate the mechanism by which bradykinin (BK) enhances prostacyclin (PGI(2)) production in human umbilical vein endothelial cells (HUVEC). BK-induced enhancement of PGI(2) synthesis was observed in a dose- and time-dependent manner, and it also increased [Ca2+](i) followed by enhancement of cytosolic phospholipase A(2) (cPLA(2)) activity. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in [Ca2+](i) and inhibited the BK-induced PGI(2) synthesis. Phorbol 12-myristate 13-acetate increased cPLA(2) activity and PGI(2) synthesis but failed to alter [Ca2+](i). BK increased cPLA(2) mRNA eightfold by 15 min, and this increase was inhibited by pretreatment with the PKC inhibitors. In response to cycloheximide pretreatment, cPLA(2) mRNA was superinduced. These results suggest that BK stimulates PGI(2) synthesis in HUVEC by activation of cPLA(2) by dual mechanisms: an elevation of [Ca2+](i) and a PKC-dependent pathway. Moreover, changes in calcium kinetics and expression of cPLA(2) mRNA may underlie the BK-induced PGI(2) enhancement in these cells. (C) 1999 Academic Press.

引用

页码：144 / 155

页数：12

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