title: Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis.
abstract: We elucidated the molecular mechanism of prostaglandin (PG) E2- and PGF2α-mediated suppression of the early phase of adipogenesis through enhanced COX-2 expression in 3T3-L1 cells. 3-Isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase which catalyzes the conversion of cAMP to AMP, enhanced the activity of protein kinase A (PKA). Dibutyryl cAMP activated PKA and enhanced the phosphorylation of cAMP response element (CRE)-binding protein (CREB). The ability of CREB binding to the CRE of the COX-2 promoter was elevated for enhancement of the expression of the COX-2 gene. CREB siRNA suppressed the expression of the COX-2 gene. Furthermore, okadaic acid, a protein phosphatase (PP) 1/2A inhibitor, suppressed the progression of adipogenesis by preventing PP1/2A-mediated suppression of CREB-dependent COX-2 expression, thus resulting in increased production of anti-adipogenic PGE2 and PGF2α. These results indicate that CREB-dependent expression of COX-2 for the production of anti-adipogenic PGs is critical for the regulation of the early phase of adipogenesis.
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: fujimori@gly.oups.ac.jp.
authors.forename: Ko
authors.initials: K
authors.lastname: Fujimori
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Yano
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kimura
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D019319:Okadaic Acid; D003994:Bucladesine; D000242:Cyclic AMP; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D010727:Phosphoric Diester Hydrolases; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine
keywords: Adipocytes; COX-2; CREB; PKA; PP1/2A; Prostaglandin