부산대학교 도서관

Hatakeyama, Daijiro, Osamu Kozawa, Masayuki Niwa, Hiroyuki Matsuno, Kanefusa Kato, Norichika Tatematsu, Toshiyuki Shibata, and Toshihiko Uematsu. Inhibition of adenylyl cyclase-cAMP system of ET-1-induced HSP27 in osteoblasts. Am J Physiol Endocrinol Metab 281: E1260-E1266, 2001.--We have previously reported that endothelin-1 (ET-1) stimulates heat shock protein (HSP) 27 induction in osteoblast-like MC3T3-E1 cells and that p38 mitogen-activated protein (MAP) kinase acts at a point downstream from protein kinase C (PKC) in HSP27 induction. In the present study, we investigated the effect of the adenylyl cyclase-cAMP system on ET-1-stimulated induction of HSP27 in MC3T3-E1 cells. Dibutyryl-cAMP (DBcAMP) dose dependently inhibited the HSP27 accumulation stimulated by ET-1. Forskolin and cholera toxin significantly suppressed the ET-1-stimulated accumulation of HSP27. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the ET-1-induced HSP27 accumulation. Forskolin reduced the p38 MAP kinase phosphorylation induced by ET-1 or 12-O-tetradecanoylphorbol-13-acetate (TPA). PGE1, an extracellular agonist that activates cAMP production, reduced the ET-1-induced HSP27 accumulation. In addition, the phosphorylation of p38 MAP kinase induced by ET-1 or TPA was suppressed by PGE1. Forskolin, DBcAMP, and PG[E.sub.1] suppressed the ET-1-stimulated increase in the mRNA level for HSP27. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in ET-1-stimulated HSP27 induction in osteoblasts and that the effect is exerted at the point between PKC and p38 MAP kinase in osteoblasts. adenosine 3',5'-cyclic monophosphate; endothelin-1; heat shock protein 27; mitogen-activated protein kinase; protein kinase C Received 2 March 2001; accepted in final form 3 August 2001