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Epoxyeicosatrienoic

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https://www.readbyqxmd.com/read/28822080/soluble-epoxide-hydrolase-inhibition-attenuates-mptp-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-involvement-of-%C3%AE-synuclein-aggregation-and-er-stress
#1
Hui-Ju Huang, Yi-Ting Wang, Hui-Ching Lin, Yi-Hsuan Lee, Anya Maan-Yuh Lin
Soluble epoxide hydrolase (sEH) is widely expressed in the mammalian brain and possesses dual enzymatic activities, including C-terminal epoxide hydrolase (C-EH) which degrades epoxyeicosatrienoic acid (EET), a beneficial arachidonic acid metabolite. In the present study, the neuroprotective effect of sEH inhibition on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using genetic and pharmacological approaches. MPTP (15 mg/kg) was intraperitoneally injected in sEH knockout (KO) mice and C57BL/6J mice as wild-type (WT) mice...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28817716/endothelial-dysfunction-in-renal-arcuate-arteries-of-obese-zucker-rats-the-roles-of-nitric-oxide-endothelium-derived-hyperpolarizing-factors-and-calcium-activated-k-channels
#2
Dandan Yin, Qianchen Wang, Xun Zhou, Ying Li
The roles of nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), and calcium-activated K+ (KCa) channels in diabetes-associated endothelial dysfunction of small renal arteries are not clear. The present study investigated acetylcholine (ACh)-induced vasorelaxation of renal arcuate arteries from obese Zucker (OZ) rats at different diabetes durations, and the relative contribution of NO, EDHF, and KCa channels to the endothelial dysfunction. OZ rats of 7 weeks (prediabetic stage), 12 weeks (early diabetic stage), and 20 weeks (late diabetic stage), and time-matched lean control rats, were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28798352/soluble-epoxide-hydrolase-inhibition-promotes-white-matter-integrity-and-long-term-functional-recovery-after-chronic-hypoperfusion-in-mice
#3
Yuxue Chen, Hao Tian, Ensheng Yao, Yeye Tian, Huaqiu Zhang, Li Xu, Zhiyuan Yu, Yongkang Fang, Wei Wang, Peng Du, Minjie Xie
Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype "combination therapy" targeting multiple mechanisms of stroke injury with a single agent...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767146/a-randomised-trial-of-effects-of-alcohol-on-cytochrome-p450-eicosanoids-mediators-of-inflammation-resolution-and-blood-pressure-in-men
#4
Anne E Barden, Venus Chavez, Michael Phillips, Emilie Mas, Lawrence J Beilin, Kevin D Croft, Trevor A Mori, Ian B Puddey
BACKGROUND: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesised by CYP450 enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs) and specialised pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)...
August 2, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28761179/soluble-epoxide-hydrolase-inhibition-protected-against-angiotensin-ii-induced-adventitial-remodeling
#5
Chi Zhou, Jin Huang, Qing Li, Jiali Nie, Xizhen Xu, Dao Wen Wang
Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28756208/activation-of-aldh1a1-in-mda-mb-468-breast-cancer-cells-that-over-express-cyp2j2-protects-against-paclitaxel-dependent-cell-death-mediated-by-reactive-oxygen-species
#6
Sarah E Allison, Yongjuan Chen, Nenad Petrovic, Jian Zhang, Kirsi Bourget, Peter I Mackenzie, Michael Murray
Cytochrome P450 2J2 (CYP2J2) expression is elevated in breast and other tumours, and is known to be protective against cytotoxic agents that may be used in cancer chemotherapy. This study evaluated the mechanisms by which MDA-MB-468 breast cancer cells that stably expressed CYP2J2 (MDA-2J2 cells) were protected against killing by the anti-cancer agent paclitaxel. Compared to control cells caspase-3/7 activation by paclitaxel was lower in MDA-2J2 cells, while cell proliferation and colony formation following paclitaxel treatment were increased...
July 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28741242/the-weakening-effect-of-soluble-epoxide-hydrolase-inhibitor-auda-on-febrile-response-to-lipopolysaccharide-and-turpentine-in-rat
#7
Jakub Piotrowski, Tomasz Jędrzejewski, Małgorzata Pawlikowska, Agata Joanna Pacuła, Jacek Ścianowski, Wiesław Kozak
A still growing body of evidence suggests the importance of epoxyeicosatrienoic acids (EETs) in the regulation of inflammatory response; therefore, drugs that stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an enzyme responsible for their metabolism, are currently under investigation. The effect of sEH inhibitors on molecular components of fever mechanism, i.e., on synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly proven; however, the hypothesis that sEH inhibitors affect febrile response has never been tested...
July 24, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28736260/soluble-epoxide-hydrolase-activation-by-s-nitrosation-contributes-to-cardiac-ischemia-reperfusion-injury
#8
Yuzhu Ding, Yazi Li, Xu Zhang, Jinlong He, Dong Lu, Xuan Fang, Yuchen Wang, Jiaxing Wang, Yuying Zhang, Xinhua Qiao, Li-Ming Gan, Chang Chen, Yi Zhu
Cardiac ischemia-reperfusion (I/R) injury always accompanies recanalization treatment for myocardial infarction. Here we found soluble epoxide hydrolase (sEH), which metabolizes cardioprotective epoxyeicosatrienoic acids into less effective diols, was rapidly activated during myocardial reperfusion in both mouse and rat models in expression-independent manner. Similar activation was mimicked by nitric oxide (NO) donor dose-dependently in vitro, along with an obvious induction of sEH S-nitrosation, a short-term post-translational modification, which diminished in sEH Cys-141-Ala mutant...
July 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28734877/enzymatic-and-free-radical-formation-of-cis-and-trans-epoxyeicosatrienoic-acids-in-vitro-and-in-vivo
#9
Theresa Aliwarga, Brianne S Raccor, Rozenn N Lemaitre, Nona Sotoodehnia, Sina A Gharib, Libin Xu, Rheem A Totah
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling properties. AA is an ω-6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds...
July 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28713267/epoxyeicosatrienoic-acid-analog-decreases-renal-fibrosis-by-reducing-epithelial-to-mesenchymal-transition
#10
Melissa Skibba, Md Abdul Hye Khan, Lauren L Kolb, Michael M Yeboah, John R Falck, Radhika Amaradhi, John D Imig
Renal fibrosis, which is a critical pathophysiological event in chronic kidney diseases, is associated with renal epithelial-to-mesenchymal transition (EMT). Epoxyeicosatrienoic acids (EETs) are Cyp epoxygenase arachidonic acid metabolites that demonstrate biological actions that result in kidney protection. Herein, we investigated the ability of 14,15-EET and its synthetic analog, EET-A, to reduce kidney fibrosis induced by unilateral ureter obstruction (UUO). C57/BL6 male mice underwent sham or UUO surgical procedures and were treated with 14,15-EET or EET-A in osmotic pump (i...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28707660/-increase-in-the-concentration-of-seh-protein-in-renal-medulla-of-isiah-rats-with-inherited-stress-induced-arterial-hypertension
#11
T O Abramova, M A Ryazanova, E V Antonov, O E Redina, A L Markel
The concentration of soluble epoxide hydrolase (sEH) protein was studied in renal medulla of adult rats from hypertensive ISIAH strain and normotensive WAG strain. The sEH is a key enzyme in metabolism of epoxyeicosatrienoic acids capable of activating endothelial NO-synthase and nitrogen oxide formation, and therefore being vasodilators. An increase in the sEH protein concentration (that we found) allows one to assume that the oxidative stress is increased in the renal medulla of hypertensive rats, and the bloodflow is decreased...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28701518/effect-of-cytochrome-p450-metabolites-of-arachidonic-acid-in-nephrology
#12
Fan Fan, Richard J Roman
Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing...
July 12, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28694203/soluble-epoxide-hydrolase-inhibitor-auda-decreases-bleomycin-induced-pulmonary-toxicity-in-mice-by-inhibiting-the-p38-smad3-pathways
#13
Xin-Wei Dong, Yong-Liang Jia, Ling-Tian Ge, Bo Jiang, Jun-Xia Jiang, Jian Shen, Ya-Chao Jin, Yan Guan, Yun Sun, Qiang-Min Xie
Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-β1-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways...
July 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28687336/polymorphisms-of-cyp2c8-cyp2c9-and-cyp2c19-and-risk-of-coronary-heart-disease-in-russian-population
#14
Alexey Polonikov, Alexander Kharchenko, Marina Bykanova, Svetlana Sirotina, Irina Ponomarenko, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Olga Bushueva, Mikhail Churnosov, Maria Solodilova
Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic acid metabolism with a wide range of biological actions in the cardiovascular system. The present study investigated whether single nucleotide polymorphisms (SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in biosynthesis of EETs, are associated with the risk of coronary heart disease (CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were included in the study...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28682418/effects-of-epoxyeicosatrienoic-acids-eets-on-retinal-macular-degeneration-in-rat-models
#15
F Mei, J-G Wang, Z-J Chen, Z-L Yuan
OBJECTIVE: Here we use a rat model to investigate the effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration along with pathological and physiological mechanisms of the disease. MATERIALS AND METHODS: Six choroidal neovascularization (CNV) rats were created with a 532 nm laser and received intravitreal injections of EETs in both eyes. On day 1, 3, 7 and 14 after photocoagulation, the thickness and area of CNV were measured with HE staining and choroidal flat mounts...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28672788/n-3-polyunsaturated-fatty-acids-decrease-the-protein-expression-of-soluble-epoxide-hydrolase-via-oxidative-stress-induced-p38-kinase-in-rat-endothelial-cells
#16
Takashi Okada, Katsutaro Morino, Fumiyuki Nakagawa, Masashi Tawa, Keiko Kondo, Osamu Sekine, Takeshi Imamura, Tomio Okamura, Satoshi Ugi, Hiroshi Maegawa
N-3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in blood vessels. Sprague-Dawley rats were fed either a control or fish oil diet for 3 weeks. Compared with the control, the fish oil diet improved acetylcholine-induced vasodilation and reduced the protein expression of soluble epoxide hydrolase (sEH), a key EET metabolic enzyme, in aortic strips...
June 24, 2017: Nutrients
https://www.readbyqxmd.com/read/28656267/epoxyeicosatrienoic-acid-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibiting-inflammatory-factors-and-pannexin-1
#17
Zhigang Liu, Yongfang Liu, Haixiao Zhou, Xiangyun Fu, Gang Hu
Epoxyeicosatrienoic acid (EET) has wide applications due to the unique biological effects of anti‑hyperlipidemia, inhibition of platelet aggregation, anti‑inflammation, anti‑cancer, anti‑lipid oxidation and the promotion of brain tissue development. The present study investigated whether EET ameliorates cerebral ischemia‑reperfusion injury (CIRI) by inhibiting inflammatory factors and pannexin. Specific pathogen‑free 7‑week‑old male Sprague‑Dawley rats were randomly divided into three groups: Sham, CIRI and EET...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28646029/editorial-focus-on-ms-h-00093-2017r1-are-the-epoxyeicosatrienoic-acids-eets-at-the-heart-of-the-b-eet-in-obesity-induced-cardiomyopathy
#18
Kevin C Dellsperger
This editorial focus discusses the accompanying paper in this issue as well as describing potential focus areas for future study in treating obesity induced cardiomyopathy.
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28616567/cyp2c19-variants-and-epoxyeicosatrienoic-acids-in-patients-with-microvascular-angina
#19
Tomonori Akasaka, Daisuke Sueta, Yuichiro Arima, Noriaki Tabata, Seiji Takashio, Yasuhiro Izumiya, Eiichiro Yamamoto, Kenichi Tsujita, Sunao Kojima, Koichi Kaikita, Ayami Kajiwara, Kazunori Morita, Kentaro Oniki, Junji Saruwatari, Kazuko Nakagawa, Seiji Hokimoto
BACKGROUND: Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on the patients with microvascular angina (MVA) caused by coronary microvascular dysfunction. METHODS AND RESULTS: We examined CYP2C19 genotypes in patients with MVA (n = 81)...
June 2017: IJC Heart & Vasculature
https://www.readbyqxmd.com/read/28576832/eet-intervention-on-wnt1-nov-and-ho-1-signaling-prevents-obesity-induced-cardiomyopathy-in-obese-mice
#20
Jian Cao, Shailendra P Singh, John McClung, Gregory Joseph, Luca Vanella, Ignazio Barbagallo, Houli Jiang, John R Falck, Michael Arad, Joseph I Shapiro, Nader G Abraham
We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on vascular function, in addition to its anti-apoptotic action, it increases insulin sensitivity and inhibits inflammation. To uncover the signaling mechanisms by which EET reduces cardiomyopathy, we hypothesized that EET infusion might ameliorate obesity-induced cardiomyopathy by improving HO-1, Wnt1, thermogenic gene levels and mitochondrial integrity in cardiac tissues and improved pericardial fat phenotype. EET reduced levels of fasting blood glucose, and pro-inflammatory adipokines including NOV signaling while increasing echocardiographic fractional shortening and O2 consumption...
June 2, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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