Fujimori Ko, Yano Mutsumi, Miyake Haruka, Kimura Hiroko
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Mol Cell Endocrinol. 2014 Mar 25;384(1-2):12-22. doi: 10.1016/j.mce.2013.12.014. Epub 2013 Dec 27.
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.
我们阐明了前列腺素（PG）E2和PGF2α通过增强3T3-L1细胞中COX-2的表达介导脂肪生成早期阶段抑制的分子机制。3-异丁基-1-甲基黄嘌呤是一种催化cAMP转化为AMP的磷酸二酯酶抑制剂，它增强了蛋白激酶A（PKA）的活性。二丁酰cAMP激活PKA并增强了cAMP反应元件（CRE）结合蛋白（CREB）的磷酸化。CREB与COX-2启动子的CRE结合能力提高，以增强COX-2基因的表达。CREB小干扰RNA（siRNA）抑制了COX-2基因的表达。此外，冈田酸是一种蛋白磷酸酶（PP）1/2A抑制剂，它通过阻止PP1/2A介导的对CREB依赖性COX-2表达的抑制来抑制脂肪生成的进程，从而导致抗脂肪生成的PGE2和PGF2α的产生增加。这些结果表明，CREB依赖性的COX-2表达以产生抗脂肪生成的PGs对于脂肪生成早期阶段的调控至关重要。
