title: Alteration of epoxyeicosatrienoic acids in the liver and kidney of cytochrome P450 4F2 transgenic mice.
abstract: Arachidonic acid (AA) can be metabolized into 20-hydroxyeicosatetraenoic acid (20-HETE) by ω-hydroxylases, and epoxyeicosatrienoic acids (EETs) by epoxygenases. The effects of EETs in cardiovascular physiology are vasodilatory, anti-inflammatory and anti‑apoptotic, which are opposite to the function to 20‑HETE. However, EETs are not stable in vivo, and are rapidly degraded to the biologically less active metabolites, dihydroxyeicosatrienoic acids, via soluble epoxide hydrolase (sEH). Western blotting, reverse transcription‑quantitative polymerase chain reaction and liquid chromatography tandem mass spectrometry were performed in order to determine target RNA and protein expression levels. In the present study, it was demonstrated that the disturbed renal 20‑HETE/EET ratio in the hypertensive cytochrome P450 4F2 transgenic mice was caused by the activation of sEH and the repression of epoxygenase activity. In addition, 20‑HETE showed an opposite regulatory effect on the endogenous epoxygenases in the liver and kidney. Given that 20‑HETE and EETs have opposite effects in multiple disease, the regulation of their formation and degradation may yield therapeutic benefits.
authors.affiliation: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Guangrui
authors.initials: G
authors.lastname: Lai
authors.affiliation: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002853:Chromatography, Liquid; D000072470:Cytochrome P450 Family 4 / Q000235:genetics* / Q000378:metabolism; D015777:Eicosanoids / Q000097:blood / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D010088:Oxidoreductases / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D015777:Eicosanoids; D007527:Isoenzymes; D016718:Arachidonic Acid; D010088:Oxidoreductases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human