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Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells.
Life Sci. 2007 Apr 17; 80(19):1768-76.LS

Abstract

The effects of sphingosine 1-phosphate (S1P) on prostaglandin I(2) (PGI(2)) production and cyclooxygenase (COX) expression in cultured rat vascular smooth muscle cells (VSMCs) were investigated. S1P stimulated PGI(2) production in a concentration-dependent manner, which was completely suppressed by NS-398, a selective COX-2 inhibitor, as determined by radioimmunoassay. S1P stimulated COX-2 protein and mRNA expressions in a concentration- and time-dependent manner, while it had no effect on COX-1 expression. S1P(2) and S1P(3) receptors mRNA were abundantly expressed in rat VSMCs. Suramin, an antagonist of S1P(3) receptor, almost completely inhibited S1P-induced COX-2 expression. Pretreatment of VSMCs with pertussis toxin (PTX) partially, but significantly inhibited S1P-induced PGI(2) production and COX-2 expression. S1P also activated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). However, neither PD 98059, a selective inhibitor of ERK activation, nor SB 203580, a selective inhibitor of p38 MAPK, had a significant inhibitory effect on S1P-induced COX-2 expression, suggesting that the MAPK activation does not play main roles in S1P-induced COX-2 induction. S1P-induced COX-2 expression was inhibited by PP2, an inhibitor of Src-family tyrosine kinase, Ca(2+) depletion, and GF 109203X, an inhibitor of protein kinase C (PKC). These results suggest that S1P stimulates COX-2 induction in rat VSMCs through mechanisms involving Ca(2+)-dependent PKC and Src-family tyrosine kinase activation via S1P(3) receptor coupled to PTX-sensitive and -insensitive G proteins.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17382352

Citation

Nodai, Akiko, et al. "Sphingosine 1-phosphate Induces Cyclooxygenase-2 Via Ca2+-dependent, but MAPK-independent Mechanism in Rat Vascular Smooth Muscle Cells." Life Sciences, vol. 80, no. 19, 2007, pp. 1768-76.
Nodai A, Machida T, Izumi S, et al. Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells. Life Sci. 2007;80(19):1768-76.
Nodai, A., Machida, T., Izumi, S., Hamaya, Y., Kohno, T., Igarashi, Y., Iizuka, K., Minami, M., & Hirafuji, M. (2007). Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells. Life Sciences, 80(19), 1768-76.
Nodai A, et al. Sphingosine 1-phosphate Induces Cyclooxygenase-2 Via Ca2+-dependent, but MAPK-independent Mechanism in Rat Vascular Smooth Muscle Cells. Life Sci. 2007 Apr 17;80(19):1768-76. PubMed PMID: 17382352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells. AU - Nodai,Akiko, AU - Machida,Takuji, AU - Izumi,Sachiko, AU - Hamaya,Yumika, AU - Kohno,Takayuki, AU - Igarashi,Yasuyuki, AU - Iizuka,Kenji, AU - Minami,Masaru, AU - Hirafuji,Masahiko, Y1 - 2007/02/20/ PY - 2006/07/13/received PY - 2007/01/12/revised PY - 2007/02/07/accepted PY - 2007/3/27/pubmed PY - 2007/6/15/medline PY - 2007/3/27/entrez SP - 1768 EP - 76 JF - Life sciences JO - Life Sci. VL - 80 IS - 19 N2 - The effects of sphingosine 1-phosphate (S1P) on prostaglandin I(2) (PGI(2)) production and cyclooxygenase (COX) expression in cultured rat vascular smooth muscle cells (VSMCs) were investigated. S1P stimulated PGI(2) production in a concentration-dependent manner, which was completely suppressed by NS-398, a selective COX-2 inhibitor, as determined by radioimmunoassay. S1P stimulated COX-2 protein and mRNA expressions in a concentration- and time-dependent manner, while it had no effect on COX-1 expression. S1P(2) and S1P(3) receptors mRNA were abundantly expressed in rat VSMCs. Suramin, an antagonist of S1P(3) receptor, almost completely inhibited S1P-induced COX-2 expression. Pretreatment of VSMCs with pertussis toxin (PTX) partially, but significantly inhibited S1P-induced PGI(2) production and COX-2 expression. S1P also activated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). However, neither PD 98059, a selective inhibitor of ERK activation, nor SB 203580, a selective inhibitor of p38 MAPK, had a significant inhibitory effect on S1P-induced COX-2 expression, suggesting that the MAPK activation does not play main roles in S1P-induced COX-2 induction. S1P-induced COX-2 expression was inhibited by PP2, an inhibitor of Src-family tyrosine kinase, Ca(2+) depletion, and GF 109203X, an inhibitor of protein kinase C (PKC). These results suggest that S1P stimulates COX-2 induction in rat VSMCs through mechanisms involving Ca(2+)-dependent PKC and Src-family tyrosine kinase activation via S1P(3) receptor coupled to PTX-sensitive and -insensitive G proteins. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/17382352/Sphingosine_1_phosphate_induces_cyclooxygenase_2_via_Ca2+_dependent_but_MAPK_independent_mechanism_in_rat_vascular_smooth_muscle_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(07)00168-3 DB - PRIME DP - Unbound Medicine ER -