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Epoxide hydrolase

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https://www.readbyqxmd.com/read/29772428/lncrna-h19-interacts-with-s-adenosylhomocysteine-hydrolase-to-regulate-line-1-methylation-in-human-lung-derived-cells-exposed-to-benzo-a-pyrene
#1
Ye Fu, Wubin Wang, Xuejing Li, Yanli Liu, Yingying Niu, Bin Zhang, Jisheng Nie, Baolong Pan, Ruisheng Wang, Jin Yang
Benzo [a]pyrene (BaP) have been demonstrated to induce lung cancer risk in humans and many different animal models, with aberrant gene methylation as one of the epigenetic errors; however, the molecular mechanisms remain unclear. Here, we used three types of human lung-derived cells with BaP exposure as a model and attempted to investigate the long non-coding RNA (lncRNA) H19/S-adenosylhomocysteine hydrolase (SAHH) pathway that regulates gene methylation in vitro exposure to BaP. Results showed that compared to the controls, BaP-treated cells H19 expressions were increased in a dose- and time-dependent manner, whereas SAHH protein expressions were decreased...
May 9, 2018: Chemosphere
https://www.readbyqxmd.com/read/29769328/proinflammatory-enzyme-soluble-epoxide-hydrolase-bridges-obesity-to-colonic-inflammation-and-potential-carcinogenesis
#2
Guang-Yu Yang
No abstract text is available yet for this article.
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29755743/epoxide-hydrolysis-as-a-model-system-for-understanding-flux-through-a-branched-reaction-scheme
#3
REVIEW
Åsa Janfalk Carlsson, Paul Bauer, Doreen Dobritzsch, Shina C L Kamerlin, Mikael Widersten
The epoxide hydrolase StEH1 catalyzes the hydrolysis of trans -methylstyrene oxide to 1-phenyl-propane-1,2-diol. The ( S , S )-epoxide is exclusively transformed into the (1 R ,2 S )-diol, while hydrolysis of the ( R , R )-epoxide results in a mixture of product enantiomers. In order to understand the differences in the stereoconfigurations of the products, the reactions were studied kinetically during both the pre-steady-state and steady-state phases. A number of closely related StEH1 variants were analyzed in parallel, and the results were rationalized by structure-activity analysis using the available crystal structures of all tested enzyme variants...
May 1, 2018: IUCrJ
https://www.readbyqxmd.com/read/29753941/an-integrated-computational-approach-of-molecular-dynamics-simulations-receptor-binding-studies-and-pharmacophore-mapping-analysis-in-search-of-potent-inhibitors-against-tuberculosis
#4
Shivangi Agarwal, Ekta Verma, Vivek Kumar, Namrita Lall, Samaresh Sau, Arun K Iyer, Sushil K Kashaw
Tuberculosis is an infectious chronic disease caused by obligate pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Although many first and second line drugs are available for its treatment, but their irrational use has adversely lead to the emerging cases of multiple drug resistant and extensively drug-resistant tuberculosis. Therefore, there is an intense need to develop novel potent analogues for its treatment. This has prompted us to develop potent analogues against TB. The Mycobacterium tuberculosis genome provides us with number of validated targets to combat against TB...
May 3, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29751149/an-inhibitor-of-soluble-epoxide-hydrolase-ameliorates-diabetes-induced-learning-and-memory-impairment-in-rats
#5
Nathani Minaz, Rema Razdan, Bruce D Hammock, Sumanta Kumar Goswami
BACKGROUND: Pharmacological inhibition of soluble epoxide hydrolase (sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with alteration in the level of neurotransmitters and oxidative stress. METHODS: Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29748789/the-polymorphism-rs2480258-within-cyp2e1-is-associated-with-different-rates-of-acrylamide-metabolism-in-vivo-in-humans
#6
Lucia Pellè, Henrik Carlsson, Monica Cipollini, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Cristina Romei, Rossella Elisei, Federica Gemignani, Margareta Törnqvist, Stefano Landi
In a recent study, we demonstrated that the variant allele of rs2480258 within intron VIII of CYP2E1 is associated with reduced levels of mRNA, protein, and enzyme activity. CYP2E1 is the most important enzyme in the metabolism of acrylamide (AA) by operating its oxidation into glycidamide (GA). AA occurs in food, is neurotoxic and classified as a probable human carcinogen. The goal of the present study was to further assess the role of rs2480258 by measuring the rate of AA > GA biotransformation in vivo...
May 10, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29735655/soluble-epoxide-hydrolase-plays-a-key-role-in-the-pathogenesis-of-parkinson-s-disease
#7
Qian Ren, Min Ma, Jun Yang, Risa Nonaka, Akihiro Yamaguchi, Kei-Ichi Ishikawa, Kenta Kobayashi, Shigeo Murayama, Sung Hee Hwang, Shinji Saiki, Wado Akamatsu, Nobutaka Hattori, Bruce D Hammock, Kenji Hashimoto
Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder, and the deposition of specific protein aggregates of α-synuclein, termed Lewy bodies, is evident in multiple brain regions of PD patients. Although there are several available medications to treat PD symptoms, these medications do not prevent the progression of the disease. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with the pathogenesis of PD. Here we found that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neurotoxicity in the mouse striatum was attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29734068/anthracene-drives-sub-cellular-proteome-wide-alterations-in-the-degradative-system-of-penicillium-oxalicum
#8
R Lucero Camacho-Morales, Cristina García-Fontana, Joaquín Fernández-Irigoyen, Enrique Santamaría, Jesús González-López, Maximino Manzanera, Elisabet Aranda
Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in polluted environments and are included in the priority list of toxic compounds. Previous studies have shown that the fungus Penicillium oxalicum, isolated from a hydrocarbon-polluted pond, has a great capability to transform different PAHs in short periods under submerged fermentation conditions. Although cytochrome p450s (CYPs) seems to be the main responsible enzyme in this process, changes in proteome profile remains poorly understood. The aim of this work was to characterise molecular disturbances in the cytosolic and microsomal sub-proteomes of P...
May 4, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29732612/synthesis-of-substituted-fluorobenzimidazoles-as-inhibitors-of-5-lipoxygenase-and-soluble-epoxide-hydrolase-for-anti-inflammatory-activity
#9
B Nandha, Sureshbabu A Ramareddy, Hazra Kuntal
A new series of 4-((5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)methyl)-benzoic acids 4a-o and 2-(5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)-2-methylpropanoic acids 8a-e were synthesized, and their inhibitory potencies against soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX) were investigated. These molecules were designed based on the combination of 5-LOX and sEH pharmacophores, resulting in hybrid analogs with potent sEH and 5-LOX inhibitory activity. Compound 4g showed remarkable activity with IC50 values of less than 1 μM (0...
May 7, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29717935/expression-of-soluble-epoxide-hydrolase-in-renal-tubular-epithelial-cells-regulates-macrophage-infiltration-and-polarization-in-iga-nephropathy
#10
Qian Wang, Yan Liang, Yingjin Qiao, Xiangya Zhao, Yi Yang, Shengnan Yang, Bing Li, Qianru Zhao, Ling Dong, Songxia Quan, Rui Tian, Zhangsuo Liu
Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in kidney remains unknown...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717038/lipidomic-profiling-reveals-soluble-epoxide-hydrolase-as-a-therapeutic-target-of-obesity-induced-colonic-inflammation
#11
Weicang Wang, Jun Yang, Jianan Zhang, Yuxin Wang, Sung Hee Hwang, Weipeng Qi, Debin Wan, Daeyoung Kim, Jia Sun, Katherine Z Sanidad, Haixia Yang, Yeonhwa Park, Jun-Yan Liu, Xinfeng Zhao, Xiaohui Zheng, Zhenhua Liu, Bruce D Hammock, Guodong Zhang
Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29703148/deletion-of-soluble-epoxide-hydrolase-attenuates-mice-hyperoxic-acute-lung-injury
#12
Li-Ping Liu, Bin Li, Tian-Kui Shuai, Lei Zhu, Yu-Min Li
BACKGROUND: Recent studies reported that soluble epoxide hydrolase (sEH) plays an important role in lung diseases. However, the role of sEH in hyperoxia-induced ALI is unclear. METHODS: ALI was induced by exposure to 100% oxygen in an airtight cage for 72 h in wild-type (WT) and sEH gene deletion (EPHX2-/- ) mice. ALI was assessed by the lung dry/wet ratio, alveolar capillary protein leak, and the infiltration of inflammatory cells in the lung. RESULTS: Hyperoxia elevated sEH activity in WT mice...
April 27, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29701466/correction-to-optimized-inhibitors-of-soluble-epoxide-hydrolase-improve-in-vitro-target-residence-time-and-in-vivo-efficacy
#13
Kin Sing Stephen Lee, Jun-Yan Liu, Karen M Wagner, Svetlana Pakhomova, Hua Dong, Christophe Morisseau, Samuel H Fu, Jun Yang, Peng Wang, Arzu Ulu, Christina A Mate, Long V Nguyen, Sung Hee Hwang, Matthew L Edin, Alexandria A Mara, Heike Wulff, Marcia E Newcomer, Darryl C Zeldin, Bruce D Hammock
No abstract text is available yet for this article.
April 27, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29662114/publisher-correction-juvenile-hormone-epoxide-hydrolase-a-promising-target-for-hemipteran-pest-management
#14
Abudourusuli Tusun, Ming Li, Xiangzhi Liang, Ting Yang, Bin Yang, Guirong Wang
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29625231/the-oxidized-linoleic-acid-metabolite-12-13-dihome-mediates-thermal-hyperalgesia-during-inflammatory-pain
#15
Béla Zimmer, Carlo Angioni, Tabea Osthues, Andy Toewe, Dominique Thomas, Sandra C Pierre, Gerd Geisslinger, Klaus Scholich, Marco Sisignano
Eicosanoids play a crucial role in inflammatory pain. However, there is very little knowledge about the contribution of oxidized linoleic acid metabolites in inflammatory pain and peripheral sensitization. Here, we identify 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), a cytochrome P450-derived linoleic acid metabolite, as crucial mediator of thermal hyperalgesia during inflammatory pain. We found 12,13-DiHOME in increased concentrations in peripheral nervous tissue during acute zymosan- and complete Freund's Adjuvant-induced inflammatory pain...
April 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29615440/inhibition-of-soluble-epoxide-hydrolase-2-ameliorates-diabetic-keratopathy-and-impaired-wound-healing-in-mouse-corneas
#16
Haijing Sun, Patrick Lee, Chenxi Yan, Nan Gao, Jiemei Wang, Xianqun Fan, Fu-Shin Yu
EPHX2 (soluble Epoxide Hydrolase 2, sEH) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and pro-fibrinolytic effectors into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, were markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type-2, mouse type-1 (STZ-induced) and/or type-2 diabetes...
April 3, 2018: Diabetes
https://www.readbyqxmd.com/read/29614409/biodegradation-of-phenanthrene-by-endophytic-fungus-phomopsis-liquidambari-in-vitro-and-in-vivo
#17
Wanqiu Fu, Man Xu, Kai Sun, Liyan Hu, Wei Cao, Chuanchao Dai, Yong Jia
Phenanthrene, as a widespread polycyclic aromatic hydrocarbons (PAHs) contaminant in vitro and in vivo of plant, has the characteristics of carcinogenicity, teratogenicity and mutagenicity. This work aimed to explore the phenanthrene metabolic mechanism by Phomopsis liquidambari in vitro, as well as the bioremediation ability through P. liquidambari-rice combination. This strain was able to use phenanthrene as source of carbon and energy to grow, more than 77% of added 50 mg L-1 phenanthrene was removed after 10 d in MSM...
March 26, 2018: Chemosphere
https://www.readbyqxmd.com/read/29614224/orally-available-soluble-epoxide-hydrolase-phosphodiesterase-4-dual-inhibitor-treats-inflammatory-pain
#18
Rene Blöcher, Karen M Wagner, Raghavender R Gopireddy, Todd R Harris, Hao Wu, Bogdan Barnych, Sung Hee Hwang, Yang K Xiang, Ewgenij Proschak, Christophe Morisseau, Bruce D Hammock
Inspired by previously discovered enhanced analgesic efficacy between soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4) inhibitors, we designed, synthesized and characterized 21 novel sEH/PDE4 dual inhibitors. The best of these displayed good efficacy in in vitro assays. Further pharmacokinetic studies of a subset of 4 selected compounds led to the identification of a bioavailable dual inhibitor N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA). In a lipopolysaccharide induced inflammatory pain rat model, MPPA rapidly increased in the blood (Tmax = 30 min; Cmax = 460 nM) after oral administration of 3 mg/kg and reduced inflammatory pain with rapid onset of action correlating with blood levels over a time course of 4 hours...
April 3, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29588470/soluble-epoxide-hydrolase-inhibition-decreases-reperfusion-injury-after-focal-cerebral-ischemia
#19
Ranran Tu, Jillian Armstrong, Kin Sing Stephen Lee, Bruce D Hammock, Adam Sapirstein, Raymond C Koehler
Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580941/increased-epoxyeicosatrienoic-acids-may-be-part-of-a-protective-mechanism-in-human-ulcerative-colitis-with-increased-cyp2j2-and-reduced-soluble-epoxide-hydrolase-expression
#20
Yi-Er Qiu, Jun Qin, Yang Luo, Shao-Lan Qin, Yi-Fei Mu, Ran Cun, Hou-Li Jiang, Jian-Jun Chen, Min-Hao Yu, Ming Zhong
BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues...
March 23, 2018: Prostaglandins & Other Lipid Mediators
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