Involvement of p42/p44 mitogen-activated protein kinase in prostaglandin f2α-stimulated induction of heat shock protein 27 in osteoblasts

✍ Scribed by Osamu Kozawa; Haruhiko Tokuda; Masaichi Miwa; Hidenori Ito; Hiroyuki Matsuno; Masayuki Niwa; Kanefusa Kato; Toshihiko Uematsu

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 179 KB
• Volume: 75
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19991215)75:4<610::aid-jcb7>3.0.co;2-8

✦ Synopsis

We previously reported that prostaglandin F 2␣ (PGF 2␣ ) activates both phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like MC3T3-E1 cells and then induces the activation of protein kinase C (PKC). In this study, we investigated the effect of PGF 2␣ on the induction of heat shock protein 27 (HSP27), a low-molecular-weight heat shock protein, in these cells. PGF 2␣ significantly induced the accumulation of HSP27 dose-dependently within the range of 10 nM to 10 µM. PGF 2␣ stimulated the increase in the levels of mRNA for HSP27. A total of 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, induced the accumulation of HSP27. The stimulative effect of PGF 2␣ was reduced in the PKC down-regulated cells. Calphostin C, a specific inhibitor of PKC, suppressed the PGF 2␣ -induced HSP27 accumulation as well as that induced by TPA. HSP27 induction by PGF 2␣ was reduced by U-73122, a phospholipase C inhibitor, or propranolol, a phosphatidic acid phosphohydrolase inhibitor. PGF 2␣ and TPA stimulated p42/p44 mitogen-activated protein (MAP) kinase. PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, suppressed the induction of HSP27 stimulated by PGF 2␣ or TPA. PD98059 and calphostin C reduced the levels of mRNA for HSP27 increased by PGF 2␣ . These results indicate that PGF 2␣ stimulates the induction of HSP27 via p42/p44 MAP kinase activation, which depends on upstream PKC activation in osteoblasts.