Involvement of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in prostaglandin F2alpha-induced heat shock protein 27 in osteoblasts.
We have reported that prostaglandin F2(alpha) (PGF2(alpha)) activates p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells, and that p44/p42 MAP kinase plays a role in the PGF2(alpha)-induced heat shock protein 27 (HSP27). In the present study, we investigated the involvement of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), a member of the MAP kinase superfamily, in PGF2(alpha)-induced HSP27 in MC3T3-E1 cells. PGF2(alpha) time dependently induced the phosphorylation of SAPK/JNK. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced the PGF2(alpha)-stimulated HSP27 accumulation. The inhibitory effect of SP600125 was dose dependent in the range between 0.1 and 30 microM. SP600125 reduced the PGF2(alpha)-increased level of HSP27 mRNA. SP600125 suppressed the phosphorylation of SAPK/JNK induced by PGF2(alpha), but did not affect the PGF2(alpha)-induced phosphorylation of p44/p42 MAP kinase. On the other hand, PD98059, a specific inhibitor of the upstream kinase of p44/p42 MAP kinase, which reduced the phosphorylation of p44/p42 MAP kinase stimulated by PGF2(alpha), had little effect on the PGF2(alpha)-induced phosphorylation of SAPK/JNK. These results strongly suggest that SAPK/JNK plays a part in PGF2(alpha)-induced HSP27 in addition to p44/p42 MAP kinase in osteoblasts.
Tokuda
H
H
Department of Pharmacology, Gifu University School of Medicine, Gifu 500-8705, Japan.
Niwa
M
M
Ishisaki
A
A
Nakajima
K
K
Ito
H
H
Kato
K
K
Kozawa
O
O
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002999:Clone Cells; D015237:Dinoprost / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects
D000873:Anthracenes; D005419:Flavonoids; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C432165:pyrazolanthrone; D015237:Dinoprost; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one