OXYSTEROL ACTIVATION OF ARACHIDONIC-ACID RELEASE AND PROSTAGLANDIN-E2 BIOSYNTHESIS IN NRK-49F CELLS IS PARTIALLY DEPENDENT ON PROTEIN-KINASE ACTIVITY

被引:13
|
作者
LAHOUA, Z
VIAL, H
MICHEL, F
DEPAULET, AC
ASTRUC, ME
机构
[1] INSERM,U58,60 RUE NAVACELLES,F-34090 MONTPELLIER,FRANCE
[2] INST BIOL,BIOCHIM LAB A,F-34000 MONTPELLIER,FRANCE
[3] UNIV MONTPELLIER 2,CNRS,URA 530,F-34060 MONTPELLIER,FRANCE
关键词
OXYSTEROL; CALCITRIOL; PHOSPHOLIPASE-A2; ARACHIDONIC ACID; PROSTAGLANDIN-E2; PHORBOL ESTER; PROTEIN KINASE-C; NRK-49F CELL;
D O I
10.1016/0898-6568(91)90032-P
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We previously demonstrated that the oxysterol potentiation of arachidonic acid release and prostaglandin biosynthesis induced by foetal calf serum activation of normal rat kidney (NRK) cells (fibroblastic clone 49F) was not related to a direct effect of oxysterols on cell free Ca2+ level. Since both Ca2+ variations and protein kinase C are involved in arachidonic acid release in some models, we looked for a possible modulation by protein kinase C in the oxysterol effect on arachidonic acid release. We show that when the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a protein kinase C activator, was added to the culture medium, the oxysterol effect on arachidonic acid release and prostaglandin synthesis clearly increased. Moreover, the effect of TPA was dose-dependent and TPA EC50 (4 x 10(-9) M) was unchanged in the presence of the oxysterol. Preincubation of cells with TPA for 24 h prevented the arachidonic acid release induced by TPA alone, whereas the oxysterol effect was decreased but not abolished. In the absence of serum, TPA and ionomycin added together induced the same noticeable (arachidonic acid) release and PGE2 synthesis as serum alone. Nevertheless, the potentiating effect of cholest-5-ene-3-beta,25-diol was much higher when serum itself was used to activate NRK cells than it was in the present serum-mimicking experimental conditions. Thus, the presence of growth factors is probably required to obtain a full oxysterol effect. We conclude that the oxysterol effect was synergistic with, but not fully dependent on, protein kinase C and Ca2+ ion fluxes, therefore oxysterols could affect earlier events triggered by serum growth factor binding to their cell membrane receptors.
引用
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页码:559 / 567
页数:9
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