p38 MAP kinase is required for vasopressin-stimulated HSP27 induction in aortic smooth muscle cells

We previously showed that arginine vasopressin (AVP) stimulates heat shock protein 27 (HSP27) induction through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined whether the mito gen-activated protein (MAP) kinase superfamily is involved in the AVP-stimu lated HSP27 induction in A10 cells. AVP stimulated the phosphorylation of p 42/p44 MAP kinase and p38 MAP kinase. On the contrary, AVP had little effec t on SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase) p hosphorylation. The HSP27 accumulation by AVP was not affected by PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, SB20 3580 and PD169316, specific inhibitors of p38 MAP kinase, suppressed the AV P-induced accumulation of HSP27. 12-O-tetradecanoylphorbol 13-acetate, an a ctivator of protein kinase C, induced accumulation of HSP27 and was not inh ibited by PD98059 but was inhibited by SB203580, Calphostin C and ET-18-OCH 3, inhibitors of protein kinase C, reduced the phosphorylation of p38 MAP k inase by AVP. SB203580 and PD169316 suppressed the AVP-increased levels in mRNA for HSP27. Dissociation of the aggregated HSP27 to the dissociated HSP 27 was induced by AVP. These results strongly suggest that p38 MAP kinase t akes part in the pathway of the AVP-stimulated induction of HSP27 in vascul ar smooth muscle cells.