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Epoxide hydrolase

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https://www.readbyqxmd.com/read/28798352/soluble-epoxide-hydrolase-inhibition-promotes-white-matter-integrity-and-long-term-functional-recovery-after-chronic-hypoperfusion-in-mice
#1
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/28789952/the-tyr113his-t-c-rs1051740-and-very-slow-phenotype-of-the-ephx1-gene-alters-mirna-26b-5p-and-mirna-1207-5p-expression-in-pregnancy-a-preliminary-study
#2
Pragalathan Naidoo, Rajen N Naidoo, Prithiksha Ramkaran, Kareshma Asharam, Anil A Chuturgoon
BACKGROUND: Environmental insults and microsomal epoxide hydrolase 1 (EPHX1) single nucleotide polymorphisms (SNPs), Tyr113His T/C rs1051740 and His139Arg A/G rs2234922, aberrantly alters microRNA expression and are linked to low birthweights (LBW). OBJECTIVES: To investigate the interplay between pollution, EPHX1 SNPs and microRNAs during pregnancy and associated LBW outcomes. METHODS: South African pregnant women (n=241) were recruited in the MACE birth cohort study in Durban...
August 5, 2017: Gene
https://www.readbyqxmd.com/read/28774830/a-physiologically-based-toxicokinetic-model-for-inhaled-ethylene-and-ethylene-oxide-in-mouse-rat-and-human
#3
Johannes Georg Filser, Dominik Klein
The olefin ethylene (ET) is the largest volume organic chemical. Mammals metabolize ET to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates hemoglobin (Hb) and DNA and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum...
July 31, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28765600/combinatorial-metabolic-engineering-of-pseudomonas-putida-kt2440-for-efficient-mineralization-of-1-2-3-trichloropropane
#4
Ting Gong, Xiaoqing Xu, You Che, Ruihua Liu, Weixia Gao, Fengjie Zhao, Huilei Yu, Jingnan Liang, Ping Xu, Cunjiang Song, Chao Yang
An industrial waste, 1,2,3-trichloropropane (TCP), is toxic and extremely recalcitrant to biodegradation. To date, no natural TCP degraders able to mineralize TCP aerobically have been isolated. In this work, we engineered a biosafety Pseudomonas putida strain KT2440 for aerobic mineralization of TCP by implantation of a synthetic biodegradation pathway into the chromosome and further improved TCP mineralization using combinatorial engineering strategies. Initially, a synthetic pathway composed of haloalkane dehalogenase, haloalcohol dehalogenase and epoxide hydrolase was functionally assembled for the conversion of TCP into glycerol in P...
August 1, 2017: Scientific Reports
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/28758642/corrigendum-role-of-phosphatase-activity-of-soluble-epoxide-hydrolase-in-regulating-simvastatin-activated-endothelial-nitric-oxide-synthase
#6
Hsin-Han Hou, Yi-Jen Liao, Sheng-Huang Hsiao, Song-Kun Shyue, Tzong-Shyuan Lee
This corrects the article DOI: 10.1038/srep13524.
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757338/soluble-epoxide-hydrolase-in-podocytes-is-a-significant-contributor-to-renal-function-under-hyperglycemia
#7
Ahmed Bettaieb, Shinichiro Koike, Ming-Fo Hsu, Yoshihiro Ito, Samah Chahed, Santana Bachaalany, Artiom Gruzdev, Miguel Calvo-Rubio, Kin Sing Stephen Lee, Bora Inceoglu, John D Imig, Jose M Villalba, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal function. The aim of this study is to investigate the contribution of sEH in podocytes to hyperglycemia-induced renal injury. MATERIALS AND METHODS: Mice with podocyte-specific sEH disruption (pod-sEHKO) were generated, and alterations in kidney function were determined under normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28745022/characterized-cantharidin-distribution-and-related-gene-expression-patterns-in-tissues-of-blister-beetles-epicauta-chinensis-laporte
#8
Ming Jiang, Shu-Min Lü, Zi-Yi Qi, Ya-Lin Zhang
Cantharidin (CTD), a terpenoid defensive toxin mainly produced by blister beetles, is widely known by its toxicity to both cancer cells and pests. However, little information is known about its biosynthesis in blister beetles. In this study, we firstly determined the CTD content in various tissues of adult blister beetles on different days after mating, and then detected the temporal and spatial expression patterns of genes related to CTD biosynthesis in Epicauta chinensis. Results revealed that the accessory gland is the source of the highest CTD production...
July 26, 2017: Insect Science
https://www.readbyqxmd.com/read/28743492/5-bromoindirubin-3-o-oxiran-2-ylmethyl-oxime-a-long-acting-anticancer-agent-and-a-suicide-inhibitor-for-epoxide-hydrolase
#9
Yoshimi Ichimaru, Takeshi Fujii, Hiroaki Saito, Makoto Sano, Taketo Uchiyama, Shinichi Miyairi
Indirubin 3'-oxime (Indox (1b)) suppresses cancer cell growth (IC50: 15μM towards HepG2 cells) and inhibits cell cycle-related kinases such as cyclin-dependent kinases and glycogen synthase kinase-3β. We have previously reported that the conjugation of 1b with oxirane, a protein-reactive component, enhanced the cytotoxic activity of Indox as determined from the IC50 value (1.7μM) of indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind (1c)). Here we prepared Epox/Ind derivatives with one or two halogen atoms or a methoxy group on the aromatic ring(s) of an Indox moiety and studied the structure-activity relationships of the substituent(s)...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28741242/the-weakening-effect-of-soluble-epoxide-hydrolase-inhibitor-auda-on-febrile-response-to-lipopolysaccharide-and-turpentine-in-rat
#10
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
#11
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/28729091/phosphatase-activity-of-soluble-epoxide-hydrolase
#12
REVIEW
Jan Kramer, Ewgenij Proschak
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that exhibits lipid epoxide hydrolase (sEH-H) and lipid phosphatase activity (sEH-P), with each being located in its own distinct domain. While the epoxide hydrolase activity is well-investigated, the role of the phosphatase domain remains unclear. This article briefly summarizes the evolution, structure and SNPs of the human sEH, with a special focus on the function and postulated role of the N-terminal domain of sEH. Furthermore, the article provides an overview of tools to study sEH-P...
July 17, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28713881/drug-delivery-and-nanoformulations-for-the-cardiovascular-system
#13
W J Geldenhuys, M T Khayat, J Yun, M A Nayeem
Therapeutic delivery to the cardiovascular system may play an important role in the successful treatment of a variety of disease state, including atherosclerosis, ischemic-reperfusion injury and other types of microvascular diseases including hypertension. In this review we evaluate the different options available for the development of suitable delivery systems that include the delivery of small organic compounds [adenosin A2A receptor agonist (CGS 21680), CYP-epoxygenases inhibitor (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy] benzoic acid), soluble epoxide hydrolase inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide), PPARγ agonist (rosiglitazone) and PPARγ antagonist (T0070907)], nanoparticles, peptides, and siRNA to the cardiovascular system...
February 2017: Res Rev Drug Deliv
https://www.readbyqxmd.com/read/28713081/gene-polymorphism-of-xenobiotic-detoxification-in-children-with-bronchial-asthma
#14
Liudmila Y Lytvynets
INTRODUCTION: Children are the most susceptible to harmful external factors due to the incomplete development of all functional body systems. The ecological situation the problem of influence of genetic and environmental factors on the pathogenesis of chronic respiratory diseases in children and its investigation is very impotent today. Among it the bronchial asthma is a leader among bronchial and pulmonary diseases caused by the influence of pneumotropic pollutants. The aim of our research was to study the phenotypic characteristics of asthma in Pre-Carpathian children with different types of allelic gene polymorphism of the first phase of xenobiotic detoxification of microsomal epoxide hydrolases (mEPHX1)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
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
#15
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/28694203/soluble-epoxide-hydrolase-inhibitor-auda-decreases-bleomycin-induced-pulmonary-toxicity-in-mice-by-inhibiting-the-p38-smad3-pathways
#16
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/28693112/association-of-prenatal-passive-smoking-and-metabolic-gene-polymorphisms-with-child-growth-from-birth-to-3years-of-age-in-the-hokkaido-birth-cohort-study-on-environment-and-children-s-health
#17
Titilola Serifat Braimoh, Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Houman Goudarzi, Thamar Ayo Yila, Atsuko Araki, Chihiro Miyashita, Hisanori Minakami, Tsuyoshi Baba, Kazuo Sengoku, Reiko Kishi
Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester≤0.21ng/mL and 0.22 to 11.48ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index...
July 6, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28672935/next-generation-sequencing-reveals-lymph-node-metastasis-associated-genetic-markers-in-colorectal-cancer
#18
Ni Xie, Yujiang Yao, Lili Wan, Ting Zhu, Litao Liu, Jianhui Yuan
Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4...
July 2017: Experimental and Therapeutic Medicine
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
#19
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/28669871/tissue-expressions-of-soluble-human-epoxide-hydrolase-2-enzyme-in-patients-with-temporal-lobe-epilepsy
#20
Merdin Lyutviev Ahmedov, Rahsan Kemerdere, Oguz Baran, Berrin Bercik Inal, Alper Gumus, Cihan Coskun, Seher Naz Yeni, Bulent Eren, Mustafa Uzan, Taner Tanriverdi
OBJECTIVE: To simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. METHODS: A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately-sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures...
June 29, 2017: World Neurosurgery
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