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Mol Cell Endocrinol. 2014 Mar 25;384(1-2):12-22. doi: 10.1016/j.mce.2013.12.014. Epub 2013 Dec 27.

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

Author information

1
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.
2
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

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.

KEYWORDS:

Adipocytes; COX-2; CREB; PKA; PP1/2A; Prostaglandin

PMID:
24378735
DOI:
10.1016/j.mce.2013.12.014
[Indexed for MEDLINE]

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