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 language | English |
|---|---|
| Pages (from-to) | 469-474 |
| Number of pages | 6 |
| Journal | Prostaglandins Leukotrienes and Essential Fatty Acids |
| Volume | 70 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 05-2004 |
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All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Cell Biology
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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 journal › Article
TY - JOUR
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
PY - 2004/5
Y1 - 2004/5
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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U2 - 10.1016/j.plefa.2003.09.003
DO - 10.1016/j.plefa.2003.09.003
M3 - Article
C2 - 15062850
AN - SCOPUS:1842633468
VL - 70
SP - 469
EP - 474
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
SN - 0952-3278
IS - 5
ER -