Arachidonic Acid Metabolism By Murine Cyp2c Isoforms

点击翻译按钮获取中文摘要

We have recently cloned several new members of the murine CYP2C subfamily, expressed the recombinant P450 proteins in E. coli, and showed that they are active in the metabolism of arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) and/or hydroxyeicosatetraenoic acids (HETEs), eicosanoids that possess potent biological activities in numerous tissues. The murine subfamily is very complex (consists of 15 genes and 4 pseudogenes). Despite the fact that these enzymes are 69-92% identical at the amino acid level, they differ markedly in their catalytic turnover and each enzyme has a unique product profile. RT-PCR and immunoblotting studies reveal that CYP2C mRNAs and proteins are abundant in both hepatic and extrahepatic tissues, and that the tissue distribution is P450 isoform-specific. We have recently identified CYP2C29 as the major CYP2C isoform in lung and demonstrated that it is highly expressed in airway epithelial cells. We have cloned the Cyp2c29 gene, characterized its intron-exon organization, and generated Cyp2c29 null mice by conventional gene targeting strategies. These mice will be studied at baseline and after selected stimuli (e.g. allergen exposure, LPS exposure) to determine the role of this P450 in lung function. We have also developed a panel of immunospecific peptide-based antibodies to the murine CYP2C isoforms so that their tissue distribution and regulation can be further investigated.