Possible involvement of p38 MAP kinase in prostaglandin E1-induced ALP activity in osteoblast-like cells

Ayako Kakita, Atsushi Suzuki, Yasunaga Ono, Yoshitaka Miura, Mitsuyasu Itoh, Yutaka Oiso

Research output: Contribution to journalArticle

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Abstract

Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E1 (PGE 1) has been reported to stimulate cAMP accumulation and to induce alkaline phosphatase (ALP) activity, a marker of differentiation, in osteoblast-like cells. Recently, we have shown that p38 mitogen-activated protein (MAP) kinase pathway regulates ALP activity in response to activation of Gi protein-coupled receptors in mouse osteoblast-like MC3T3-E1 cells (Suzuki et al., Endocrinology 140 (1999) 3177). In the present study, we investigated whether p38 MAP kinase is involved in ALP activation by PGE1 in MC3T3-E1 osteoblast-like cells. PGE1 dose-dependently enhanced ALP activities in the concentration range between 1 nM and 1 μM in MC3T3-E1 cells. SB203580, a specific inhibitor of p38 MAP kinase, blocked the increase in ALP activity induced by PGE1. Further analysis with western blotting suggested that PGE1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt2CAMP, a permeable analogue of cAMP, and forskolin, which directly activates adenylate cyclase, also induced an increase in Tyr phosphorylation of p38 MAP kinase. H-89, a potent inhibitor of protein kinase A (PKA), significantly suppressed PGE 1-induced Tyr phosphorylation of p38 MAP kinase. The results of this study suggest that PGE1 stimulates p38 MAP kinase through the activation of PKA, resulting in the enhancement of ALP activity.

Original languageEnglish
Pages (from-to)469-474
Number of pages6
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume70
Issue number5
DOIs
Publication statusPublished - 05-2004

Fingerprint

Alprostadil
Osteoblasts
p38 Mitogen-Activated Protein Kinases
Alkaline Phosphatase
Phosphorylation
Tyrosine
Chemical activation
Cyclic AMP-Dependent Protein Kinases
Endocrinology
Differentiation Antigens
Colforsin
Bone Resorption
Adenylyl Cyclases
Osteogenesis
Prostaglandins
Bone
Western Blotting
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

Cite this

Kakita, Ayako ; Suzuki, Atsushi ; Ono, Yasunaga ; Miura, Yoshitaka ; Itoh, Mitsuyasu ; Oiso, Yutaka. / Possible involvement of p38 MAP kinase in prostaglandin E1-induced ALP activity in osteoblast-like cells. In: Prostaglandins Leukotrienes and Essential Fatty Acids. 2004 ; Vol. 70, No. 5. pp. 469-474.
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Possible involvement of p38 MAP kinase in prostaglandin E1-induced ALP activity in osteoblast-like cells. / Kakita, Ayako; Suzuki, Atsushi; Ono, Yasunaga; Miura, Yoshitaka; Itoh, Mitsuyasu; Oiso, Yutaka.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 70, No. 5, 05.2004, p. 469-474.

Research output: Contribution to journalArticle

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T1 - Possible involvement of p38 MAP kinase in prostaglandin E1-induced ALP activity in osteoblast-like cells

AU - Kakita, Ayako

AU - Suzuki, Atsushi

AU - Ono, Yasunaga

AU - Miura, Yoshitaka

AU - Itoh, Mitsuyasu

AU - Oiso, Yutaka

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N2 - Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E1 (PGE 1) has been reported to stimulate cAMP accumulation and to induce alkaline phosphatase (ALP) activity, a marker of differentiation, in osteoblast-like cells. Recently, we have shown that p38 mitogen-activated protein (MAP) kinase pathway regulates ALP activity in response to activation of Gi protein-coupled receptors in mouse osteoblast-like MC3T3-E1 cells (Suzuki et al., Endocrinology 140 (1999) 3177). In the present study, we investigated whether p38 MAP kinase is involved in ALP activation by PGE1 in MC3T3-E1 osteoblast-like cells. PGE1 dose-dependently enhanced ALP activities in the concentration range between 1 nM and 1 μM in MC3T3-E1 cells. SB203580, a specific inhibitor of p38 MAP kinase, blocked the increase in ALP activity induced by PGE1. Further analysis with western blotting suggested that PGE1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt2CAMP, a permeable analogue of cAMP, and forskolin, which directly activates adenylate cyclase, also induced an increase in Tyr phosphorylation of p38 MAP kinase. H-89, a potent inhibitor of protein kinase A (PKA), significantly suppressed PGE 1-induced Tyr phosphorylation of p38 MAP kinase. The results of this study suggest that PGE1 stimulates p38 MAP kinase through the activation of PKA, resulting in the enhancement of ALP activity.

AB - Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E1 (PGE 1) has been reported to stimulate cAMP accumulation and to induce alkaline phosphatase (ALP) activity, a marker of differentiation, in osteoblast-like cells. Recently, we have shown that p38 mitogen-activated protein (MAP) kinase pathway regulates ALP activity in response to activation of Gi protein-coupled receptors in mouse osteoblast-like MC3T3-E1 cells (Suzuki et al., Endocrinology 140 (1999) 3177). In the present study, we investigated whether p38 MAP kinase is involved in ALP activation by PGE1 in MC3T3-E1 osteoblast-like cells. PGE1 dose-dependently enhanced ALP activities in the concentration range between 1 nM and 1 μM in MC3T3-E1 cells. SB203580, a specific inhibitor of p38 MAP kinase, blocked the increase in ALP activity induced by PGE1. Further analysis with western blotting suggested that PGE1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt2CAMP, a permeable analogue of cAMP, and forskolin, which directly activates adenylate cyclase, also induced an increase in Tyr phosphorylation of p38 MAP kinase. H-89, a potent inhibitor of protein kinase A (PKA), significantly suppressed PGE 1-induced Tyr phosphorylation of p38 MAP kinase. The results of this study suggest that PGE1 stimulates p38 MAP kinase through the activation of PKA, resulting in the enhancement of ALP activity.

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