Vol. 281, Issue 6, E1260-E1266, December 2001
Inhibition by adenylyl cyclase-cAMP system of ET-1-induced HSP27
in osteoblasts
Daijiro
Hatakeyama,
Osamu
Kozawa,
Masayuki
Niwa,
Hiroyuki
Matsuno,
Kanefusa
Kato,
Norichika
Tatematsu,
Toshiyuki
Shibata, and
Toshihiko
Uematsu
Departments of Pharmacology and Oral and Maxillo-Facial Surgery,
Gifu University School of Medicine, Gifu 500 - 8705; and
Department of Biochemistry, Aichi Human Service Center, Institute for
Developmental Research, Kasugai, Aichi 480-0392, Japan
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 PGE1
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
