Department of Chemical Engineering , Pennsylvania State University , University Park 16802 .
J Cell Physiol 150 : 552-8 ( 1992)
Abstract
Our previous studies have shown that steady shear stress causes a transient increase of platelet-derived growth factor ( PDGF ) A and B chain mRNA levels in human umbilical vein endothelial cells ( HUVEC ) .
In the present study , we elucidated the signaling pathway of shear stress in HUVEC by examining the roles of protein kineses , intracellular calcium , cyclooxygenase , and guanine nucleotide-binding proteins ( G proteins ) in the PDGF gene induction by shear .
The protein kinase C inhibitors , H7 and staurosporine , strongly inhibited the shear-induced PDGF gene expression in HUVEC .
In contrast , HA1004 , a cAMP- and cGMP-dependent protein kinases inhibitor , was only slightly inhibitory .
BAPTA/AM , an intracellular calcium chelator , partially ( 50% ) inhibited the shear-induced PDGF gene expression .
The cyclooxygenase inhibitors , ibuprofen and indomethacin , were slightly inhibitory .
A 35-50% inhibition of shear-induced PDGF gene expression was found with GDP-beta-S , an inhibitor of G proteins .
These results suggest that shear-induced PDGF gene expression in HUVEC is mainly mediated by protein kinase C activation and requires intracellular calcium .
Furthermore , G proteins seem to be involved in this process , whereas prostaglandin synthesis via cyclooxygenase pathway is not .
We propose a mechanism of shear-induced PDGF gene expression in HUVEC : Shear stress , either directly or indirectly ( G protein-mediated ) , enhances the membrane phosphoinositide turnover via phospholipase C , producing diacylglycerol , an activator of protein kinase C. The activated protein kinase C then triggers the subsequent PDGF gene expression .