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CYP2J2

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https://www.readbyqxmd.com/read/29759885/terfenadone-is-a-strong-inhibitor-of-cyp2j2-present-in-the-human-liver-and-intestinal-microsomes
#1
Eunyoung Lee, Ju-Hyun Kim, Jong Cheol Shon, Zhexue Wu, Hyun Ji Kim, Minsik Gim, Taeho Lee, Kwang-Hyeon Liu
Cytochrome P450 2J2 (CYP2J2) is involved in the metabolism of drugs, including albendazole, astemizole, ebastine, and endogenous substrates. In a previous study, we used recombinant CYP2J2 and determined whether danazol, hydroxyebastine, telmisartan, and terfenadone inhibited CYP2J2 by using four representative CYP2J2 substrates, namely albendazole, astemizole, ebastine, and terfenadine. In this study, we evaluated the inhibitory potential of these four chemicals on human liver and intestinal microsomes, which are commonly used in a reaction phenotyping study...
March 15, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29715548/posttranslational-regulation-of-cyp2j2-by-nitric-oxide
#2
Ji Won Park, Choon-Myung Lee, Joan S Cheng, Edward T Morgan
Nitric oxide (NO) is an essential signaling molecule in the body, regulating numerous biological processes. Beside its physiological roles, NO affects drug metabolism by modulating the activity and/or expression of cytochrome P450 enzymes. Previously, our lab showed that NO generation caused by inflammatory stimuli results in CYP2B6 degradation via the ubiquitin-proteasome pathway. In the current study, we tested the NO-mediated regulation of CYP2J2 that metabolizes arachidonic acids to bioactive epoxyeicosatrienoic acids, as well as therapeutic drugs such as astemizole and ebastine...
April 28, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29695613/cytochrome-p450-2j2-potential-role-in-drug-metabolism-and-cardiotoxicity
#3
Meetal Satishkumar Solanki, Amy Pointon, Barry C Jones, Karl E Herbert
Drug-induced cardiotoxicity may be modulated by endogenous arachidonic acid (AA) derived metabolites known as epoxyeicosatrienoic acids (EETs) synthesised by cytochrome P450 2J2 (CYP2J2). The biological effects of EETs including its protective effects on inflammation and vasodilation are diverse due, in part, to their ability to act on a variety of cell types. In addition, CYP2J2 metabolises both exogenous and endogenous substrates and is involved in phase I metabolism of a variety of structurally diverse compounds including some antihistamines, anti-cancer agents and immunosuppressants...
April 25, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29689453/cross-talk-of-cannabinoid-and-endocannabinoid-metabolism-is-mediated-via-human-cardiac-cyp2j2
#4
William R Arnold, Austin T Weigle, Aditi Das
Phytocannabinoids have well-known cardiovascular implications. For instance, Δ9-tetrahydrocannabinol (Δ9-THC), the principal component of cannabis, induces tachycardia in humans. In order to understand the impact of phytocannabinoids on human cardiovascular health, there is a need to study the metabolism of phytocannabinoids by cardiac cytochromes p450 (CYPs). CYP2J2, the primary CYP of cardiomyocytes, is responsible for the metabolism of the endocannabinoid, anandamide (AEA), into cardioprotective epoxides (EET-EAs)...
April 7, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29689254/inhibitory-effects-of-danshen-components-on-cyp2c8-and-cyp2j2
#5
Mei-Juan Xu, Li-Feng Jiang, Ting Wu, Ji-Hong Chu, Yi-Dan Wei, Ji-Ye Aa, Guang-Ji Wang, Hai-Ping Hao, Wen-Zheng Ju, Ping Li
The use of Chinese herbal medicines and natural products has become increasingly popular in both China and Western societies as an alternative medicine for the treatment of diseases or as a health supplement. Danshen, the dried root of Salvia miltiorrhiza (Fam.Labiatae), which is rich in phenolic acids and tanshinones, is a widely used herbal medicine for the treatment of cardio-cerebrovascular diseases. The goal of this study was to examine the inhibitory effects of fifteen components derived from Danshen on CYP2C8 and CYP2J2, which are expressed both in human liver and cardiovascular systems...
April 21, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29656108/epoxygenase-inactivation-exacerbates-diet-and-aging-associated-metabolic-dysfunction-resulting-from-impaired-adipogenesis
#6
Antoni Olona, Ximena Terra, Jeong-Hun Ko, Carme Grau-Bové, Montserrat Pinent, Anna Ardevol, Ana Garcia Diaz, Aida Moreno-Moral, Matthew Edin, David Bishop-Bailey, Darryl C Zeldin, Timothy J Aitman, Enrico Petretto, Mayte Blay, Jacques Behmoaras
OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions...
March 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29655687/the-inhibitory-potential-of-broussochalcone-a-for-the-human-cytochrome-p450-2j2-isoform-and-its-anti-cancer-effects-via-foxo3-activation
#7
See-Hyoung Park, Jongsung Lee, Jong Cheol Shon, Nguyen Minh Phuc, Jun Goo Jee, Kwang-Hyeon Liu
BACKGROUND: Broussonetia papyrifera (L.) Ventenat, a traditional medicinal herb, has been applied as a folk medicine to treat various diseases. Broussochalcone A (BCA), a chalcone compound isolated from the cortex of Broussonetia papyrifera (L.) Ventenat, exhibits several biological activities including potent anti-oxidant, antiplatelet, and cytotoxic effects. PURPOSE: The purpose of this study is to elucidate the inhibitory effect of BCA against CYP2J2 enzyme which is predominantly expressed in human tumor tissues and carcinoma cell lines...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29629756/an-emerging-pathway-of-doxorubicin-cardiotoxicity-mediated-through-cyp2j2
#8
William R Arnold, Aditi Das
No abstract text is available yet for this article.
April 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/29614520/risk-factors-for-higher-than-expected-residual-rivaroxaban-plasma-concentrations-in-real-life-patients
#9
Alexander Kaserer, Andreas Schedler, Alexander Jetter, Burkhardt Seifert, Donat R Spahn, Philipp Stein, Jan-Dirk Studt
INTRODUCTION:  Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients...
April 3, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29602797/formation-of-both-heme-and-apoprotein-adducts-contributes-to-the-mechanism-based-inactivation-of-human-cyp2j2-by-17%C3%AE-ethynylestradiol
#10
Hsia-Lien Lin, Haoming Zhang, Paul F Hollenberg
17α-Ethynylestradiol (EE), a major component of many oral contraceptives, affects the activities of a number of the human cytochrome P450 (CYP) enzymes. Here, we characterized the effect of EE on CYP2J2, a major human CYP isoform which participates in metabolism of arachidonic acid. EE inactivated the hydroxyebastine carboxylation activity of CYP2J2 in a reconstituted system. The loss of activity is time- and concentration-dependent and requires NADPH. K I and k inact values for the inactivation were 3.6 μM and 0...
March 30, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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
#11
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
https://www.readbyqxmd.com/read/29552858/-effect-of-ophiopogonin-d-in-resisting-vascular-endothelial-cell-apoptosis-induced-by-ang%C3%A2-through-up-regulating-cyp2j2-eets
#12
Xiao-Yan Huang, Yu-Guang Wang, Yi Wang, Yue Gao
This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH)...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29433675/plant-natural-product-plumbagin-presents-potent-inhibitory-effect-on-human-cytochrome-p450-2j2-enzyme
#13
Jian Lu, Daozhi Liu, Xiaojing Zhou, Ang Chen, Zhenran Jiang, Xiyun Ye, Mingyao Liu, Xin Wang
BACKGROUND: Cytochrome P450 2J2 (CYP2J2) is not only highly expressed in many kinds of human tumors, but also promotes tumor cell growth via regulating the metabolism of arachidonic acids. CYP2J2 inhibitors can significantly reduce proliferation, migration and promote apoptosis of tumor cells by inhibiting epoxyeicosatrienoic acids (EETs) biosynthesis. Therefore screening CYP2J2 inhibitors is a significant way for the development of anti-cancer drug. PURPOSE: The aim of this study was to identify a new CYP2J2 inhibitor from fifty natural compounds obtained from plants...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29427791/cyp2j2-derived-eets-attenuated-ethanol-induced-myocardial-dysfunction-through-inducing-autophagy-and-reducing-apoptosis
#14
Chi Zhou, Jin Huang, Qing Li, Chenao Zhan, Xizhen Xu, Xu Zhang, Ding Ai, Yi Zhu, Zheng Wen, Dao Wen Wang
Chronic excessive drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, where ethanol toxicity plays an essential role. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the cardiovascular system, but their role in alcoholic cardiomyopathy is elusive. This study was designed to evaluate the effects and mechanisms of CYP2J2 gene delivery on ethanol-induced myocardial dysfunction with focus on autophagy and apoptosis...
March 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29363498/a-novel-in-vitro-experimental-system-for-the-evaluation-of-drug-metabolism-cofactor-supplemented-permeabilized-cryopreserved-human-hepatocytes-metmax%C3%A2-cryopreserved-human-hepatocytes
#15
Albert P Li, Ming-Chih David Ho, Kirsten Amaral, Carol Loretz
We report here a novel experimental system - MetMax™ cryopreserved human hepatocytes (MMHH), for in vitro drug metabolism studies. MMHH consist of cofactor-supplemented permeabilized cryopreserved human hepatocytes. The use procedures for MMHH are significantly simplified from that for conventional cryopreserved human hepatocytes (CCHH): 1. Storage at -80o C instead of in liquid nitrogen; 2. Usage directly after thawing without centrifugation and microscopic evaluation of cell density and viability and cell density adjustment...
January 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29343610/cyp2j2-expression-in-adult-ventricular-myocytes-protects-against-external-and-drug-induced-ros-toxicity
#16
Eric A Evangelista, Rozenn Lemaitre, Nona Sotoodehnia, Sina Gharib, Rheem A Totah
CYP2J2 is a drug metabolizing enzyme that is highly expressed in adult ventricular myocytes. It is responsible for the bioactivation of arachidonic acid (AA) into epoxyeicosatrienoic acids (EETs). EETs are biologically active signaling compounds that protect against disease progression, particularly in cardiovascular diseases. As a drug-metabolizing enzyme, CYP2J2 is susceptible to drug interactions that could lead to cardiotoxicity. Previously, CYP2J2 has been shown to be resistant to induction by canonical CYP inducers such as phenytoin and rifampin...
January 17, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29318723/endothelium-specific-cyp2j2-overexpression-attenuates-age-related-insulin-resistance
#17
Yan Yang, Ruolan Dong, Zhihui Chen, Danli Hu, Menglu Fu, Ying Tang, Dao Wen Wang, Xizhen Xu, Ling Tu
Ample evidences demonstrate that cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, and cardiovascular protective effects. In this study, we investigated the effects of endothelium-specific CYP2J2 overexpression on age-related insulin resistance and metabolic dysfunction. Endothelium-specific targeting of the human CYP epoxygenase, CYP2J2, transgenic mice (Tie2-CYP2J2-Tr mice) was utilized. The effects of endothelium-specific CYP2J2 overexpression on aging-associated obesity, inflammation, and peripheral insulin resistance were evaluated by assessing metabolic parameters in young (3 months old) and aged (16 months old) adult male Tie2-CYP2J2-Tr mice...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29233455/genetic-variation-of-cytochrome-p450-in-uyghur-chinese-population
#18
Guangzhao Qi, Duolu Li, Xiaojian Zhang
Interindividual and interethnic variability of drug responses could be attributed to the differences of genetic polymorphisms in the drug metabolizing enzymes and transporters genes among the populations. Here we reviewed the studies of genetic variations in Uyghur Chinese of fifteen CYP450 genes including CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP2W1, CYP3A4, CYP3A5, CYP4A11, and CYP17A1, which totally covered 277 variants. We also collected the data of 277 variants covered in our study in two extensive population sequencing projects, the International HapMap Project (Hap-Map) and the 1000 Genomes Project and compared them with the data of Uyghur Chinese...
February 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29200270/arachidonic-acid-metabolism-by-human-cardiovascular-cyp2j2-is-modulated-by-doxorubicin
#19
William R Arnold, Javier L Baylon, Emad Tajkhorshid, Aditi Das
Doxorubicin (DOX) is a chemotherapeutic that is used in the treatment of a wide variety of cancers. However, it causes cardiotoxicity partly because of the formation of reactive oxygen species. CYP2J2 is a human cytochrome P450 that is strongly expressed in cardiomyocytes. It converts arachidonic acid (AA) into four different regioisomers of epoxyeicosatrienoic acids (EETs). Using kinetic analyses, we show that AA metabolism by CYP2J2 is modulated by DOX. We show that cytochrome P450 reductase, the redox partner of CYP2J2, metabolizes DOX to 7-deoxydoxorubicin aglycone (7-de-aDOX)...
December 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/29098037/role-of-cytochrome-p450-2j2-on-cell-proliferation-and-resistance-to-an-anticancer-agent-in-hepatocellular-carcinoma-hepg2-cells
#20
Geun Hye Hwang, So Mi Park, Ho Jae Han, Kyoung Min Baek, Joong Sun Kim, Woochul Chang, Ho Jin Lee, Seung Pil Yun, Jung Min Ryu, Min Young Lee
The present study examined the role of human cytochrome P450 2J2 (CYP2J2) on cell proliferation and resistance to an anticancer agent using stable hepatocellular carcinoma HepG2 cells overexpressing CYP2J2. Overexpression of CYP2J2 significantly increased HepG2 cell proliferation and the expression levels of cell cycle regulatory proteins, including cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4. CYP2J2-overexpressing HepG2 cells exhibited high levels of Akt phosphorylation compared with those observed in wild-type HepG2 cells...
November 2017: Oncology Letters
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