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CYP2J2

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https://www.readbyqxmd.com/read/28587983/ophiopogonin-d-and-eets-ameliorate-ang-ii-induced-inflammatory-responses-via-activating-ppar%C3%AE-in-huvecs
#1
Xiaoyan Huang, Yuguang Wang, Zhaoyan Zhang, Yuan Wang, Xiangmei Chen, Yi Wang, Yue Gao
CYP2J2 is highly expressed in cardiovascular tissue including the heart and vascular endothelial cells. CYP2J2 and the EETs have been shown owning diverse biological effects. Our previous study found that ophiopogonin D (OP-D) suppressed drug-induced endoplasmic reticulum (ER) stress by upregulating the levels of CYP2J3/EETs in cardiomyocytes. The aim of this research was to investigate whether CYP2J2/EETs-PPARα pathway involved in endothelium protective effects of OP-D in human umbilical vein endothelial cells (HUVECs)...
June 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28554983/cyp2j2-metabolites-epoxyeicosatrienoic-acids-attenuate-angii-induced-cardiac-fibrotic-response-by-targeting-g%C3%AE-12-13
#2
Zuowen He, Yong Yang, Zheng Wen, Chen Chen, Xizhen Xu, Yanfang Zhu, Yan Wang, Dao Wen Wang
Arachidonic acid-cytochrome P450 2J2-epoxyeicosatrienoic acids (AA-CYP2J2-EETs) metabolic pathway has been identified protective in cardiovascular system. This study explored effects of AA-CYP2J2-EETs metabolic pathway on cardiac fibrosis from perspective of cardiac fibroblast and underlying mechanisms. In vivo studies, eight-week-old male CYP2J2 transgenic mice (aMHC-CYP2J2-Tr) and littermates were infused with angiotensin II (Ang II) or saline for 2 weeks. Results showed that CYP2J2 overexpression increased EETs production...
May 29, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28488585/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#3
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28461575/lky-047-first-selective-inhibitor-of-cytochrome-p450-2j2
#4
Nguyen Minh Phuc, Zhexue Wu, Yuseok O, Jee-Hyun Lee, Sangtaek Oh, Gyu-Yong Song, Kwang-Hyeon Liu
Highly selective cytochrome P450 CYP2J2 (CYP2J2) inhibitors suitable for reaction phenotyping are currently not available. (7S)-(+)-(4-Nitro-phenyl)-acrylic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (LKY-047), a decursin derivative, was synthesized, and its inhibitor potencies toward CYP2J2 as well as other cytochrome P450 (P450) enzymes in human liver microsomes (HLM) were evaluated. LKY-047 was demonstrated to be a strong competitive inhibitor of CYP2J2-mediated astemizole O-demethylase and terfenadine hydroxylase activity, with Ki values of 0...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28440284/cyp2j2-and-its-metabolites-eets-attenuate-insulin-resistance-via-regulating-macrophage-polarization-in-adipose-tissue
#5
Meiyan Dai, Lujin Wu, Peihua Wang, Zheng Wen, Xizhen Xu, Dao Wen Wang
Macrophages in adipose tissue are associated with obesity-induced low-grade inflammation, which contributed to insulin resistance and the related metabolic diseases. Previous studies demonstrated the beneficial effects of epoxyeicosatrienoic acids (EETs) on metabolic disorders and inflammation. Here we investigated the effects of CYP2J2-EETs-sEH metabolic pathway on insulin resistance in mice and the potential mechanisms. High fat diet (HFD)-induced obesity caused metabolic dysfunction with more weight gain, elevated glucose and lipids levels, impaired glucose tolerance and insulin sensitivity, while increase in EETs level by rAAV-mediated CYP2J2 overexpression, administration of sEH inhibit TUPS or EETs infusion significantly attenuated these metabolic disorders...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#6
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28374982/angiotensin-ii-receptor-blockers-inhibit-the-generation-of-epoxyeicosatrienoic-acid-from-arachidonic-acid-in-recombinant-cyp2c9-cyp2j2-and-human-liver-microsomes
#7
Asuna Senda, Yuji Mukai, Toru Hayakawa, Yuka Kato, Erik Eliasson, Anders Rane, Takaki Toda, Nobuo Inotsume
Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), have cardioprotective effects including anti-inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2, and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50 ) of AA metabolism was losartan < telmisartan < irbesartan < candesartan < olmesartan < valsartan via CYP2C9, and telmisartan < irbesartan < olmesartan < losartan < candesartan and valsartan via CYP2J2...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28328948/vascular-endothelial-overexpression-of-human-cyp2j2-tie2-cyp2j2-tr-modulates-cardiac-oxylipin-profiles-and-enhances-coronary-reactive-hyperemia-in-mice
#8
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, John R Falck, Mohammed A Nayeem
Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases. EETs and HETEs often have opposite biologic effects; EETs are vasodilatory and protect against ischemia/reperfusion injury, while ω-terminal HETEs are vasoconstrictive and cause vascular dysfunction. Other oxylipins, such as epoxyoctadecaenoic acids (EpOMEs), hydroxyoctadecadienoic acids (HODEs), and prostanoids also have varied vascular effects...
2017: PloS One
https://www.readbyqxmd.com/read/28316087/influence-of-abcc2-cyp2c8-and-cyp2j2-polymorphisms-on-tacrolimus-and-mycophenolate-sodium-based-treatment-in-brazilian-kidney-transplant-recipients
#9
Fabiana D V Genvigir, Alvaro M Nishikawa, Claudia R Felipe, Helio Tedesco-Silva, Nagilla Oliveira, Antony B C Salazar, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario D C Hirata
STUDY OBJECTIVE: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose-adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. DESIGN: Pharmacogenetic analysis of patients enrolled in a previously published study...
March 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28272236/association-of-cyp2j2-gene-polymorphisms-with-ischemic-stroke-and-stroke-subtypes-in-chinese-population
#10
Si-Yang Wang, Peng-Fei Xing, Chun-Yang Zhang, Ben-Qiang Deng
BACKGROUND AND PURPOSE: Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28237650/inhibition-and-inactivation-of-human-cyp2j2-implications-in-cardiac-pathophysiology-and-opportunities-in-cancer-therapy
#11
REVIEW
Aneesh Karkhanis, Yanjun Hong, Eric Chun Yong Chan
Extrahepatic cytochrome P450 enzymes (CYP450) are pivotal in the metabolism of endogenous substrates and xenobiotics. CYP2J2 is a major cardiac CYP450 and primarily metabolizes polyunsaturated fatty acids such as arachidonic acid to cardioactive epoxyeicosatrienoic acids. Due to its role in endobiotic metabolism, CYP2J2 has been actively studied in recent years with the focus on its biological functions in cardiac pathophysiology. Additionally, CYP2J2 metabolizes a number of xenobiotics such as astemizole and terfenadine and is potently inhibited by danazol and telmisartan...
July 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28237619/glutamate-affects-the-production-of-epoxyeicosanoids-within-the-brain-the-up-regulation-of-brain-cyp2j-through-the-mapk-creb-signaling-pathway
#12
Mingzhou Liu, Quanfei Zhu, Jinhua Wu, Xuming Yu, Mingbai Hu, Xianfei Xie, Zheqiong Yang, Jing Yang, Yu-Qi Feng, Jiang Yue
Glutamate is the major excitatory neurotransmitter in the brain, and chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative diseases. We investigated the effects of glutamate at concentrations lower than the usual extrasynaptic concentrations on the production of epoxyeicosanoids mediated by brain CYP2J. Glutamate increased CYP2J2 mRNA levels in astrocytes in a dose-dependent manner, while an antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) attenuated the glutamate-induced increases in CYP2J2 levels by glutamate...
April 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28160853/identification-of-acetylshikonin-as-the-novel-cyp2j2-inhibitor-with-anti-cancer-activity-in-hepg2-cells
#13
See-Hyoung Park, Nguyen Minh Phuc, Jongsung Lee, Zhexue Wu, Jieun Kim, Hyunkyoung Kim, Nam Doo Kim, Taeho Lee, Kyung-Sik Song, Kwang-Hyeon Liu
BACKGROUND: Acetylshikonin is one of the biologically active compounds derived from the root of Lithospermum erythrorhizon, a medicinal plant with anti-cancer and anti-inflammation activity. Although there have been a few previous reports demonstrating that acetylshikonin exerts anti-cancer activity in vitro and in vivo, it is still not clear what is the exact molecular target protein of acetylshikonin in cancer cells. PURPOSE: The purpose of this study is to evaluate the inhibitory effect of acetylshikonin against CYP2J2 enzyme which is predominantly expressed in human tumor tissues and carcinoma cell lines...
January 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28126315/identification-of-cytochrome-p450-isoforms-involved-in-the-metabolism-of-syl930-a-selective-s1pr1-agonist-acting-as-a-potential-therapeutic-agent-for-autoimmune-encephalitis
#14
Jiaqi Mi, Manman Zhao, Shu Yang, Yufei Jia, Yan Wang, Baolian Wang, Jing Jin, Xiaojian Wang, Qiong Xiao, Jinping Hu, Yan Li
Syl930 is a novel sphingosine-1-phosphate receptor subtype 1 (S1PR1) agonist for the treatment of autoimmune encephalitis with promising receptor selectivity and little risk of bradycardia. Syl930 could be reversibly converted to its phosphorylated metabolite, acting as the active form to provide therapeutic effects, but eliminated principally in the form of oxidative metabolites. The aim of the present study was to identify the cytochrome P450 isoforms (CYPs) responsible for the oxidative metabolism of Syl930...
July 14, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28053220/application-of-static-modeling-in-the-prediction-of-in-vivo-drug-drug-interactions-between-rivaroxaban-and-anti-arrhythmic-agents-based-on-in-vitro-inhibition-studies
#15
Eleanor Jing Yi Cheong, Janice Jia Ni Goh, Yanjun Hong, Gopalakrishnan Venkatesan, Yuanjie Liu, Gigi Ngar Chee Chiu, Pipin Kojodjojo, Eric Chun Yong Chan
Rivaroxaban, a direct Factor Xa inhibitor, is indicated for stroke prevention in non-valvular atrial fibrillation (AF). Studies have revealed that the clearance of rivaroxaban is largely attributed to CYP3A4, CYP2J2 metabolism and P-gp efflux pathways. Amiodarone and dronedarone are anti-arrhythmic agents employed in AF management. Amiodarone, dronedarone and their major metabolites, N-desethylamiodarone (NDEA) and N-desbutyldronedarone (NDBD) demonstrate inhibitory effects on CYP3A4 and CYP2J2 with FDA recommended probe substrates...
January 4, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28030819/hyperhomocysteinemia-results-from-and-promotes-hepatocellular-carcinoma-via-cyp450-metabolism-by-cyp2j2-dna-methylation
#16
Donghong Zhang, Jinli Lou, Xu Zhang, Lin Zhang, Fei Wang, Danfei Xu, Na Niu, Yidong Wang, Yue Wu, Wei Cui
Hyperhomocysteinemia (HHcy) can result from liver disease or dysfunction and further alters intracellular lipid metabolism. Cytochrome P450 (CYP) arachidonic acid epoxygenases are expressed in human cancers and promote cancer metastasis. This study explored the interaction of Hcy and CYP450 metabolism in hepatocellular carcinoma (HCC). The levels of 4-epoxyeicosatrienoic acid (EET) isomers and their generative enzyme CYP2J2 level as well as intracellular Hcy level were higher in 42 cases of HCC than in paired non-tumor tissue...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28000856/cyp2j2-participates-in-atherogenesis-by-mediating-cell-proliferation-migration-and-foam-cell-formation
#17
Rui Li, Yuan Zhang, Huacheng Yan, Hua Xiao, Yunjun Ruan, Jian Qiu, Lei Shi
Atherosclerosis (AS) is a common pathological basis for the development of various cardiovascular and cerebrovascular diseases, however, currently, no effective treatment against AS has been established. It has previously been suggested that intravascular cytochrome P450 (CYP) oxidase is involved in the pathogenesis of AS. The present study investigated the role of cytochrome P450, family 2, subfamily J, polypeptide 2 (CYP2J2), the most common subtype of CYP oxidase in the human body, in the occurrence and development of AS...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27992998/asymmetric-binding-and-metabolism-of-polyunsaturated-fatty-acids-pufas-by-cyp2j2-epoxygenase
#18
William R Arnold, Javier L Baylon, Emad Tajkhorshid, Aditi Das
Cytochrome P450 (CYP) 2J2 is the primary epoxygenase in the heart and is responsible for the epoxidation of arachidonic acid (AA), an ω-6 polyunsaturated fatty acid (PUFA), into anti-inflammatory epoxide metabolites. It also epoxidizes other PUFAs such as docosahexaenoic acid (DHA), linoleic acid (LA), and eicosapentaenoic acid (EPA). Herein, we have performed detailed thermodynamic and kinetic analyses to determine how DHA, LA, and EPA modulate the metabolism of AA by CYP2J2. We use the Nanodisc system to stabilize CYP2J2 and its redox partner, CYP reductase (CPR)...
December 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27796781/computational-modelling-of-the-binding-of-arachidonic-acid-to-the-human-monooxygenase-cyp2j2
#19
G Proietti, K K Abelak, D Bishop-Bailey, A Macchiarulo, I Nobeli
An experimentally determined structure for human CYP2J2-a member of the cytochrome P450 family with significant and diverse roles across a number of tissues-does not yet exist. Our understanding of how CYP2J2 accommodates its cognate substrates and how it might be inhibited by other ligands thus relies on our ability to computationally predict such interactions using modelling techniques. In this study we present a computational investigation of the binding of arachidonic acid (AA) to CYP2J2 using homology modelling, induced fit docking (IFD) and molecular dynamics (MD) simulations...
November 2016: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/27791151/targeting-cyp2j-to-reduce-paclitaxel-induced-peripheral-neuropathic-pain
#20
Marco Sisignano, Carlo Angioni, Chul-Kyu Park, Sascha Meyer Dos Santos, Holger Jordan, Maria Kuzikov, Di Liu, Sebastian Zinn, Stephan W Hohman, Yannick Schreiber, Béla Zimmer, Mike Schmidt, Ruirui Lu, Jing Suo, Dong-Dong Zhang, Stephan M G Schäfer, Martine Hofmann, Ajay S Yekkirala, Natasja de Bruin, Michael J Parnham, Clifford J Woolf, Ru-Rong Ji, Klaus Scholich, Gerd Geisslinger
Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 and increased concentrations of its linoleic acid metabolite 9,10-EpOME (9,10-epoxy-12Z-octadecenoic acid) in dorsal root ganglia (DRGs) of paclitaxel-treated mice as a model of CIPNP. The lipid sensitizes TRPV1 ion channels in primary sensory neurons and causes increased frequency of spontaneous excitatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic nerves and DRGs, and a reduction in mechanical and thermal pain hypersensitivity...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
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