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(Hypertension. 2000;35:673.)
© 2000 American Heart Association, Inc.

Scientific Contributions

p38 MAP Kinase Is Required for Vasopressin-Stimulated HSP27 Induction in Aortic Smooth Muscle Cells

Takeshi Ito; Osamu Kozawa; Kumiko Tanabe; Masayuki Niwa; Hiroyuki Matsuno; Noboru Sakai; Hidenori Ito; Kanefusa Kato; Toshihiko Uematsu

From the Department of Pharmacology (T.I., K.T., M.N., H.M., T.U.) and Department of Neurosurgery (T.I., N.S.), Gifu University School of Medicine, Gifu, Japan; and the Department of Biochemistry (H.I., K.K.), Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.

Correspondence to Osamu Kozawa, MD, PhD, Department of Pharmacology, Gifu University School of Medicine, Gifu 500-8705, Japan.

Abstract—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 mitogen-activated protein (MAP) kinase superfamily is involved in the AVP-stimulated HSP27 induction in A10 cells. AVP stimulated the phosphorylation of p42/p44 MAP kinase and p38 MAP kinase. On the contrary, AVP had little effect on SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase) phosphorylation. The HSP27 accumulation by AVP was not affected by PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. SB203580 and PD169316, specific inhibitors of p38 MAP kinase, suppressed the AVP-induced accumulation of HSP27. 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C, induced accumulation of HSP27 and was not inhibited by PD98059 but was inhibited by SB203580. Calphostin C and ET-18-OCH₃, inhibitors of protein kinase C, reduced the phosphorylation of p38 MAP kinase by AVP. SB203580 and PD169316 suppressed the AVP-increased levels in mRNA for HSP27. Dissociation of the aggregated HSP27 to the dissociated HSP27 was induced by AVP. These results strongly suggest that p38 MAP kinase takes part in the pathway of the AVP-stimulated induction of HSP27 in vascular smooth muscle cells.

Key Words: protein kinases • vasopressins • aorta • muscle, smooth, vascular

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