title: Adenylyl cyclase-cAMP system inhibits thrombin-induced HSP27 in vascular smooth muscle cells.
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.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Gifu 501-1194, Japan.
authors.forename: Kouseki
authors.initials: K
authors.lastname: Hirade
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Niwa
authors.forename: Akira
authors.initials: A
authors.lastname: Ishisaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Katagiri
authors.forename: Kanefusa
authors.initials: K
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017931:DNA Primers; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D006360:Heat-Shock Proteins; D009281:Naphthalenes; C061465:calphostin complex; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin; D000262:Adenylyl Cyclases; D019311:Staurosporine; D000225:Adenine; D013755:Tetradecanoylphorbol Acetate