Adenylyl cyclase-cAMP system inhibits thrombin-induced HSP27 in vascular smooth muscle cells

✍ Scribed by Kouseki Hirade; Kumiko Tanabe; Masayuki Niwa; Akira Ishisaki; Keiichi Nakajima; Mitsuhiro Nakamura; Tadashi Sugiyama; Yoshihiro Katagiri; Kanefusa Kato; Osamu Kozawa

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 305 KB
• Volume: 94
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20309

✦ Synopsis

Abstract

We previously reported that thrombin stimulates the induction of heat shock protein (HSP) 27 via p38 mitogen‐activated protein (MAP) kinase activation in aortic smooth muscle A10 cells. In the present study, we investigated the effect of the adenylyl cyclase‐cAMP system on the thrombin‐stimulated induction of HSP27 in A10 cells. Forskolin, a direct activator of adenylyl cyclase, reduced the thrombin‐induced p38 MAP kinase phosphorylation, and significantly suppressed the thrombin‐stimulated accumulation of HSP27. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the HSP27 accumulation. Furthermore, dibutyryl‐cAMP (DBcAMP), a permeable analog of cAMP, significantly suppressed the accumulation of HSP27. On the other hand, calphostin C, an inhibitor of protein kinase C (PKC), reduced the thrombin‐induced p38 MAP kinase phosphorylation, and significantly suppressed the thrombin‐stimulated accumulation of HSP27. Moreover, forskolin reduced the p38 MAP kinase phosphorylation induced by the 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a PKC‐activating phorbol ester, and significantly suppressed the TPA‐stimulated accumulation of HSP27. These results indicate that adenylyl cyclase‐cAMP system has an inhibitory role in thrombin‐stimulated HSP27 induction in aortic smooth muscle cells, and the effect seems to be exerted on the thrombin‐induced PKC‐ p38 MAP kinase signaling pathway. © 2004 Wiley‐Liss, Inc.