PMID- 27878278 OWN - NLM STAT- MEDLINE DCOM- 20170406 LR - 20181119 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 14 IP - 6 DP - 2016 Dec TI - Alteration of epoxyeicosatrienoic acids in the liver and kidney of cytochrome P450 4F2 transgenic mice. PG - 5739-5745 LID - 10.3892/mmr.2016.5962 [doi] AB - Arachidonic acid (AA) can be metabolized into 20-hydroxyeicosatetraenoic acid (20-HETE) by omega-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. FAU - Zhang, Bijun AU - Zhang B AD - Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Lai, Guangrui AU - Lai G AD - Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Liu, Xiaoliang AU - Liu X AD - Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Zhao, Yanyan AU - Zhao Y AD - Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. LA - eng PT - Journal Article DEP - 20161123 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Eicosanoids) RN - 0 (Isoenzymes) RN - 27YG812J1I (Arachidonic Acid) RN - EC 1.- (Oxidoreductases) RN - EC 1.14.14.1 (Cytochrome P450 Family 4) RN - EC 1.14.14.78 (CYP4F2 protein, human) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - EC 3.3.2.10 (EPHX2 protein, human) SB - IM MH - Animals MH - Arachidonic Acid/*metabolism MH - Chromatography, Liquid MH - Cytochrome P450 Family 4/*genetics/metabolism MH - Eicosanoids/blood/metabolism MH - Epoxide Hydrolases/genetics/metabolism MH - Gene Expression Profiling MH - Humans MH - Hydroxylation MH - Isoenzymes MH - Kidney/*drug effects/*metabolism MH - Liver/*drug effects/*metabolism MH - Male MH - Metabolic Syndrome/genetics/metabolism MH - Metabolomics/methods MH - Mice MH - Mice, Transgenic MH - Middle Aged MH - Oxidative Stress/genetics MH - Oxidoreductases/metabolism MH - Tandem Mass Spectrometry EDAT- 2016/11/24 06:00 MHDA- 2017/04/07 06:00 CRDT- 2016/11/24 06:00 PHST- 2015/09/15 00:00 [received] PHST- 2016/09/26 00:00 [accepted] PHST- 2016/11/24 06:00 [pubmed] PHST- 2017/04/07 06:00 [medline] PHST- 2016/11/24 06:00 [entrez] AID - 10.3892/mmr.2016.5962 [doi] PST - ppublish SO - Mol Med Rep. 2016 Dec;14(6):5739-5745. doi: 10.3892/mmr.2016.5962. Epub 2016 Nov 23.