BASIC FGF ACTIVATES PHOSPHOLIPASE-D IN ENDOTHELIAL-CELLS IN THE ABSENCE OF INOSITOL-LIPID HYDROLYSIS

被引:43
作者
AHMED, A
PLEVIN, R
SHOAIBI, MA
FOUNTAIN, SA
FERRIANI, RA
SMITH, SK
机构
[1] UNIV STRATHCLYDE,DEPT PHYSIOL & PHARMACOL,GLASGOW G1 1XW,SCOTLAND
[2] BOURN HALL CLIN,CAMBRIDGE CB3 7TR,ENGLAND
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1994年 / 266卷 / 01期
基金
英国惠康基金;
关键词
VASCULAR ENDOTHELIAL CELLS; PHORBOL ESTER; PROTEIN KINASE C; TYROSINE KINASE; CELL PROLIFERATION; MITOGENESIS; FIBROBLAST GROWTH FACTOR;
D O I
10.1152/ajpcell.1994.266.1.C206
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
In the absence of inositol-lipid hydrolysis, mitogenic concentrations of basic fibroblast growth factor (bFGF) stimulated phosphatidylbutanol formation in the presence of butan-1-ol in [H-3]myristate-labeled human umbilical vascular endothelial (HUVE) cells, indicating that the fibroblast growth factor receptor was able to couple to the activation of phospholipase D (PLD). The ability of bFGF and 12-O-tetradecanoylphorbol-13-acetate (TPA) to stimulate PLD activity was completely abolished in cells pretreated with 400 nM TPA for 48 h to downregulate protein kinase C (PKC). bFGF-stimulated PLD activity was inhibited by genistein (5 mu M; P < 0.02) and the PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 5 mu M; P < 0.001) as well as by the removal of calcium from extracellular environment. bFGF induced DNA synthesis in a dose-dependent manner, and pretreatment of cells with H-7 inhibited the mitogenic activity of bFGF. These results indicate that activation of PKC is responsible for bFGF-induced PLD activation and the mitogenic activity of bFGF in HUVE cells. A coupled PLD/3-sn-phosphatidate phosphohydrolase pathway may play a role in the regulation of endothelial cell proliferation.
引用
收藏
页码:C206 / C212
页数:7
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