Abstract
Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E 1 (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 PGE 1 in MC3T3-E1 osteoblast-like cells. PGE 1 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 PGE 1 . Further analysis with western blotting suggested that PGE 1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt 2 CAMP, 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 PGE 1 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 - 01-01-2004 |
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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, 01.01.2004, 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 - 2004/1/1
Y1 - 2004/1/1
N2 - Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E 1 (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 PGE 1 in MC3T3-E1 osteoblast-like cells. PGE 1 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 PGE 1 . Further analysis with western blotting suggested that PGE 1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt 2 CAMP, 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 PGE 1 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 E 1 (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 PGE 1 in MC3T3-E1 osteoblast-like cells. PGE 1 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 PGE 1 . Further analysis with western blotting suggested that PGE 1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt 2 CAMP, 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 PGE 1 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 -