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Am J Physiol Heart Circ Physiol 283: H941-H948, 2002; doi:10.1152/ajpheart.00060.2001
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Vol. 283, Issue 3, H941-H948, September 2002

Thrombin stimulates dissociation and induction of HSP27 via p38 MAPK in vascular smooth muscle cells

Kouseki Hirade1,3, Osamu Kozawa1, Kumiko Tanabe1,2, Masayuki Niwa1, Hiroyuki Matsuno1, Yutaka Oiso4, Shigeru Akamatsu2, Hidenori Ito5, Kanefusa Kato5, Yoshihiro Katagiri3, and Toshihiko Uematsu1

Departments of 1 Pharmacology and 2 Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Gifu 500-8705; 3 Department of Pharmacy, Gifu University Hospital, Gifu 500-8705; 4 First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466-8560; and 5 Department of Biochemistry, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan

We investigated the effects of thrombin on the induction of heat shock proteins (HSP) 70 and 27, and the mechanism behind the induction in aortic smooth muscle A10 cells. Thrombin increased the level of HSP27 but had little effect on the level of HSP70. Thrombin stimulated the accumulation of HSP27 dose dependently between 0.01 and 1 U/ml and cycloheximide reduced the accumulation. Thrombin stimulated an increase in the level of HSP27 mRNA and actinomycin D suppressed the thrombin-increased mRNA level. Thrombin induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The HSP27 accumulation by thrombin was reduced by SB-203580 and PD-169316 but not by SB-202474. SB-203580 and PD-169316 suppressed the thrombin-induced phosphorylation of p38 MAPK. SB-203580 reduced the thrombin-increased level of HSP27 mRNA. Dissociation of the aggregated HSP27 to the dissociated HSP27 was induced by thrombin. Dissociation was inhibited by SB-203580. Thrombin induced the phosphorylation of HSP27 and the phosphorylation was suppressed by SB-203580. These results indicate that thrombin stimulates not only the dissociation of HSP27 but also the induction of HSP27 via p38 MAPK activation in aortic smooth muscle cells.

serine protease; A20 cell; intracellular signaling


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