Mechanism of prostaglandin E2-stimulated heat shock protein 27 induction in osteoblast-like MC3T3-E1 cells

• Published in: Journal of endocrinology Vol. 172; no. 2; pp. 271 - 281
• Main Authors: Tokuda, H, Kozawa, O, Niwa, M, Matsuno, H, Kato, K, Uematsu, T
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.02.2002; Portland Press
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Butadienes - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cell Line; Chelating Agents - pharmacology; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Enzyme Activation; Enzyme Inhibitors - pharmacology; Estrenes - pharmacology; Flavonoids - pharmacology; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Heat-Shock Proteins; HSP70 Heat-Shock Proteins - metabolism; Imidazoles - pharmacology; Mice; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Naphthalenes - antagonists & inhibitors; Naphthalenes - pharmacology; Neoplasm Proteins - metabolism; Nitriles - pharmacology; Osteoblasts - drug effects; Osteoblasts - metabolism; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Pyridines - pharmacology; Pyrrolidinones - pharmacology; Staurosporine - pharmacology; Stimulation, Chemical; Time Factors; Type C Phospholipases - antagonists & inhibitors
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1720271

We investigated the effect of prostaglandin E2 (PGE2) on the induction of heat shock protein 27 (HSP27) and HSP70, and the mechanism behind the induction in osteoblast-like MC3T3-E1 cells. PGE2 time-dependently increased the level of HSP27 without affecting the level of HSP70. PGE2 stimulated the accumulation of HSP27 dose-dependently in the range between 10 nM and 10 microM. PGE2 stimulated the increase in the level of the mRNA for HSP27. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), suppressed the PGE2-induced HSP27 accumulation. The effect of PGE2 on HSP27 accumulation was reduced in the PKC down-regulated cells. BAPTA/AM, a chelator of intracellular Ca2+, or TMB-8, an inhibitor of intracellular Ca2+ mobilization, reduced the accumulation of HSP27 induced by PGE2. Dibutyryl cAMP had little effect on the basal level of HSP27. PGE2 induced the phosphorylation of both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. PD98059 and U-0126, inhibitors of the upstream kinase of p44/p42 MAP kinase, reduced the accumulation of HSP27 induced by PGE2. SB203580, a specific inhibitor of p38 MAP kinase, suppressed the HSP27 accumulation induced by PGE2. U-73122, an inhibitor of phospholipase C, and calphostin C reduced the PGE2-induced phosphorylation of both p44/p42 MAP kinase and p38 MAP kinase. These results indicate that PGE2 stimulates the induction of HSP27 through PKC-dependent activations of both p44/p42 MAP kinase and p38 MAP kinase in osteoblasts.