Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis

•IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression. We elucidated the molecular mechanism of prostaglandin (...

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Veröffentlicht in:Molecular and cellular endocrinology 2014-03, Vol.384 (1-2), p.12-22
Hauptverfasser: Fujimori, Ko, Yano, Mutsumi, Miyake, Haruka, Kimura, Hiroko
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Sprache:eng
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Zusammenfassung:•IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression. 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.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2013.12.014