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Protein Kinase C and protein tyrosine Kinase mediate lipopolysaccharide- and cytokine-induced nitric oxide formationin vascular smooth muscle cells of rats

HAN Ya- Ling, KANG Jian, LI Shao Hua

Department of Cardiology，General Hospital of ShenyanA，The Institute of Cardiovascular Research，PLA, 110016 Department of Pathology and Laboratory Medicine，Robert Wood Johnson Medical School，New Jersey 08854，USA

Abstract

Rat aorta media，adventitia and cultured vascular smooth muscle cells(VSMCs) were used in this stndy to identfy the source of nitric oxide(NO) generation from various cell types of vascular tissues and to elucidate the mechanisms involved in NO formation .Treatment of vascular media and VSMCs with lipopolysaccharide(LPS) or cytokines[tumor necrosis factor alpha(TNF。)
and interleukirrl beta(IL- Ip)]resulted in a dose-dependent increase of NO release .Inducible nitric oxide synthase(iNOS) in the stimulated VSMCs was significantly upregulated as shown by Western blot analysis .Protein kinase C(PK()inhibitor 1一(5- isoquinolinesulfonyl)一2- methylpiperazine(117) prevented LPSL，TNF a- and IL 1 [r induce d NO production，whereas N(2- guanidinoethyl)一5-isoquinoline- sulfonamide(HA1004)，an H7 analogue with little activity towards PK(，had no inhibition effect .The role of PKC in
LPS- and cytokine-induced changes on NO formation was confirmed by using another structurally distinct PKC inhibitor chelerythrine.Treatment of VSMCs with protein tyrosine kinase(PT)nhibitor genistein or tyrphostin AG18 also reduced the NO production evoked by LPS，TNF a or IL 1 [3，which was ssociated with inhibition of iNO8 protein expression .In contrast，PKC inhibitorythrine did not affect iNOS expression .These results suggest that PTK mediates LPS- and cytokine-induced NO formation by upregulation of iNO8 expression .PKC may be involved in the post translational modification of iNO8 or the regulation of the availability of iNOS substrates and cofactors.

Key words: Nitric oxide; nrntein kinase C;nrntein tvrmine kinase ; smooth muscle

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Citing This Article：

HAN Ya- Ling, KANG Jian, LI Shao Hua. Protein Kinase C and protein tyrosine Kinase mediate lipopolysaccharide- and cytokine-induced nitric oxide formationin vascular smooth muscle cells of rats . Acta Physiol Sin 2003; 55 (3): (in Chinese with English abstract).