The epoxygenases CYP2J2 activates the nuclear receptor PPARalpha in vitro and in vivo

环氧化酶CYP2J2在体内和体外激活核受体PPARalpha

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作者:Jessica A Wray, Mary C Sugden, Darryl C Zeldin, Gemma K Greenwood, Salma Samsuddin, Laura Miller-Degraff, J Alyce Bradbury, Mark J Holness, Timothy D Warner, David Bishop-Bailey

Background

Peroxisome proliferator-activated receptors (PPARs) are a family of three (PPARalpha, -beta/delta, and -gamma) nuclear receptors. In particular, PPARalpha is involved in regulation of fatty acid metabolism, cell growth and inflammation. PPARalpha mediates the cardiac fasting response, increasing fatty acid metabolism, decreasing glucose utilisation, and is the target for the fibrate lipid-lowering class of drugs. However, little is known regarding the endogenous generation of PPAR ligands. CYP2J2 is a lipid metabolising cytochrome P450, which produces anti-inflammatory mediators, and is considered the major epoxygenase in the human heart. Methodology/principal findings: Expression of CYP2J2 in vitro

Significance

Our results establish that CYP2J2 produces PPARalpha ligands in vitro and in vivo, and suggests that lipid metabolising CYPs are prime candidates for the integration of global lipid changes to transcriptional signalling events.

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