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https://www.readbyqxmd.com/read/28110484/upregulation-of-20-hete-synthetic-cytochrome-p450-isoforms-by-oxygen-glucose-deprivation-in-cortical-neurons
#1
Hui Zhang, John R Falck, Richard J Roman, David R Harder, Raymond C Koehler, Zeng-Jin Yang
20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor, is a cytochrome P450 (CYP) 4A/4F-derived metabolite of arachidonic acid. Inhibition of 20-HETE synthesis protects brain from ischemic injury. However, that protection is not associated with changes in cerebral blood flow. The present study examined whether CYP4A isoforms are expressed in neurons, whether they produce 20-HETE in neurons, and whether neuronally derived 20-HETE exerts direct neurotoxicity after oxygen-glucose deprivation (OGD)...
January 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28110334/muscone-induces-cyp1a2-and-cyp3a4-enzyme-expression-in-l02-human-liver-cells-and-cyp1a2-and-cyp3a11-enzyme-expression-in-kunming-mice
#2
Sha Liu, Yujie Cheng, Menglin Rao, Mi Tang, Zhi Dong
AIM: To examine the effect of synthetic muscone on the expression of CYP1A2 and CYP3A4 enzymes in human liver L02 cells and in the liver tissue of Kunming mice. METHODS: The L02 hepatic cell line was used to study the effect of low (10-4 μmol/L), middle (10-3 μmol/L), and high concentrations (10-2 μmol/L) of muscone on the expression of CYP1A2 and CYP3A4 enzymes. In addition, the cytochrome P450 (CYP) expression was investigated in Kunming mice after the administration of 10 mg/kg (low), 50 mg/kg (middle), and 100 mg/kg (high) dose of muscone for 6 days...
January 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28110013/dna-damage-and-translational-response-during-detoxification-from-copper-exposure-in-a-wild-population-of-chironomus-riparius
#3
Paola Bernabò, Matteo Gaglio, Francesco Bellamoli, Gabriella Viero, Valeria Lencioni
Copper is one of the predominant components of pesticides employed in agriculture and known to be highly toxic once it reaches aquatic organisms. The impact of sublethal concentrations of this metal on wild insects is not yet completely understood. Studies addressing alterations in different levels of gene expression are still lacking. We previously demonstrated that in a wild population of Chironomus riparius, HSP and CYP families of genes were up-regulated at the transcriptional level after copper exposure...
January 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28109855/heterologous-expression-and-characterization-of-plant-taxadiene-5%C3%AE-hydroxylase-cyp725a4-in-escherichia-coli
#4
John Edward Rouck, Bradley Walters Biggs, Amogh Kambalyal, William R Arnold, Marjan De Mey, Parayil Kumaran Ajikumar, Aditi Das
Taxadiene-5α-Hydroxylase (CYP725A4) is a membrane-bound plant cytochrome P450 that catalyzes the oxidation of taxadiene to taxadiene-5α-ol. This oxidation is a key step in the production of the valuable cancer therapeutic and natural plant product, taxol. In this work, we report the bacterial expression and purification of six different constructs of CYP725A4. All six of these constructs are N-terminally modified and three of them are fused to cytochrome P450 reductase to form a chimera construct. The construct with the highest yield of CYP725A4 protein was then selected for substrate binding and kinetic analysis...
January 18, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28109684/increase-in-the-systemic-exposure-of-primary-metabolites-of-midazolam-in-rat-arising-from-cyp-inhibition-or-hepatic-dysfunction
#5
Tsubasa Hasegawa, Satomi Nakanishi, Keiko Minami, Haruki Higashino, Makoto Kataoka, Yoshihisa Shitara, Shinji Yamashita
The main purpose of this study is to demonstrate the possibility of increase in the systemic exposure of drug metabolites by CYP-inhibition or acute hepatitis. Midazolam (MDZ) was used as a model substrate of CYP3A and 1-aminobenzotriazole (ABT) was used as a CYP-inhibitor. After oral pretreatment with ABT, MDZ was intravenously injected to rats and the plasma profiles of MDZ and its primary metabolites, 1'-hydroxy MDZ and 4-hydroxy MDZ, were observed. In the ABT-pretreatment rats, plasma AUCs of both metabolites were much larger than those in control rats, demonstrating a higher systemic exposure of metabolites under CYP-inhibited condition...
November 23, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28105288/discovery-of-spirocyclic-aldosterone-synthase-inhibitors-as-potential-treatments-for-resistant-hypertension
#6
Whitney L Petrilli, Scott B Hoyt, Clare London, Daniel McMasters, Andreas Verras, Mary Struthers, Doris Cully, Thomas Wisniewski, Ning Ren, Charlene Bopp, Andrea Sok, Qing Chen, Ying Li, Elaine Tung, Wei Tang, Gino Salituro, Ian Knemeyer, Bindhu Karanam, Joseph Clemas, Gaochao Zhou, Jack Gibson, Carrie Ann Shipley, Douglas J MacNeil, Ruth Duffy, James R Tata, Feroze Ujjainwalla, Amjad Ali, Yusheng Xiong
Herein we report the discovery and hit-to-lead optimization of a series of spirocyclic piperidine aldosterone synthase (CYP11B2) inhibitors. Compounds from this series display potent CYP11B2 inhibition, good selectivity versus related CYP enzymes, and lead-like physical and pharmacokinetic properties.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28105234/interaction-of-cyclophilin-a-with-a-novel-binding-protein-sr-25-and-characterization-of-their-expression-pattern-in-chinese-hepatocellular-carcinoma-patients
#7
Jian Chen, Ning Li, Peiwen Lian, Jiahui Wang, Peng Li, Zhaohua Gong, Lixin Jiang
Cyclophilin (Cyp) A has been reported to be overexpressed in the majority of cancer cells, including hepatocellular carcinoma (HCC). However, the biological functions of CypA in HCC are far from being understood. To determine the biological functions of CypA in HCC, the present study screened human fetal liver complementary DNA for proteins interacting with CypA using the yeast two-hybrid system. A nuclear protein, serine/arginine-rich (SR)-25, was isolated as a novel CypA-binding protein that is distinct from those previously described in the literature...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101244/celery-extract-inhibits-mouse-cyp2a5-and-human-cyp2a6-activities-via-different-mechanisms
#8
Xiao Deng, Qianghong Pu, Erhao Wang, Chao Yu
Human cytochrome P450 (CYP) 2A6 participates in the metabolism of nicotine and precarcinogens, thus the deliberate inhibition of CYP2A6 may reduce cigarette consumption and therefore reduce the risk of developing the types of cancer associated with smoking. The inhibitory effects and mechanisms of celery (Apium graveolens) extract on mouse CYP2A5 and human CYP2A6 activity remain unclear. These effects were investigated in mouse and human liver microsomes using coumarin 7-hydroxylation in a probe reaction. Celery extract reduced CYP2A5 and CYP2A6 activities in vitro in a dose-dependent manner...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099882/the-35-year-odyssey-of-beta-blockers-in-cirrhosis-any-gender-difference-in-sight
#9
REVIEW
Maria Antonella Burza, Hanns-Ulrich Marschall, Laura Napoleone, Antonio Molinaro
Cirrhosis is the end-stage of chronic liver disease and leads to the development of portal hypertension and its complications such as esophagogastric varices. Non-selective beta blockers (NSBB) are the keystone for the treatment of portal hypertension since the 1980s and, over the decades, several studies have confirmed their beneficial effect on the prevention of variceal (re)bleeding. Pharmacological studies showed effects of gender, sex hormones, oral contraceptives, and pregnancy on cytochrome P450 (CYPs) enzymes that metabolise NSBB, suggesting that gender differences might exist in the effect of NSBB...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28097004/rifampicin-decreases-exposure-to-sublingual-buprenorphine-in-healthy-subjects
#10
Nora M Hagelberg, Mari Fihlman, Tuija Hemmilä, Janne T Backman, Jouko Laitila, Pertti J Neuvonen, Kari Laine, Klaus T Olkkola, Teijo I Saari
Buprenorphine is mainly metabolized by the cytochrome P450 (CYP) 3A4 enzyme. The aim of this study was to evaluate the role of first-pass metabolism in the interaction of rifampicin and analgesic doses of buprenorphine. A four-session paired cross-over study design was used. Twelve subjects ingested either 600 mg oral rifampicin or placebo once daily in a randomized order for 7 days. In the first part of the study, subjects were given 0.6-mg (placebo phase) or 0.8-mg (rifampicin phase) buprenorphine sublingually on day 7...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#11
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28089731/investigation-of-polymorphisms-in-genes-involved-in-estrogen-metabolism-in-menstrual-migraine
#12
Heidi G Sutherland, Morgane Champion, Amelie Plays, Shani Stuart, Larisa M Haupt, Alison Frith, E Anne MacGregor, Lyn R Griffiths
Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism...
January 13, 2017: Gene
https://www.readbyqxmd.com/read/28089686/simulations-of-cytochrome-p450-3a4-mediated-drug-drug-interactions-by-simple-two-compartment-model-assisted-static-method
#13
Katsumi Iga, Akiko Kiriyama
In order to predict cytochrome P450 3A4 (CYP3A4)-mediated drug-drug interactions (DDIs), a simple two-compartment model assisted, overall inhibition-activity (Ai, overall) method was derived based upon two concepts. One concept was that the increase in blood victim-level and fold increase in the area under the blood victim-level curve (AUCR) produced by DDI are determined entirely by Ai, overall, the hepatic availability of the victim and fraction of urinary excreted unchanged victim, where Ai, overall is determined by the perpetrator-specific CYP isoform inhibition activities (Ai,CYPs, DDI predictor-1) and victim-specific fractional CYP isoform contributions (fm,CYPs, predictor-2)...
January 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28089047/cypome-of-the-conifer-pathogen-heterobasidion-irregulare-inventory-phylogeny-and-transcriptional-analysis-of-the-response-to-biocontrol
#14
Anthony C Mgbeahuruike, Andriy Kovalchuk, Wimal Ubhayasekera, David R Nelson, Jagjit S Yadav
The molecular mechanisms underlying the interaction of the pathogen, Heterobasidion annosum s.l., the conifer tree and the biocontrol fungus, Phlebiopsis gigantea have not been fully elucidated. Members of the cytochrome P450 (CYP) protein family may contribute to the detoxification of components of chemical defence of conifer trees by H. annosum during infection. Additionally, they may also be involved in the interaction between H. annosum and P. gigantea. A genome-wide analysis of CYPs in Heterobasidion irregulare was carried out alongside gene expression studies...
February 2017: Fungal Biology
https://www.readbyqxmd.com/read/28088650/assessing-the-identity-and-expression-level-of-the-cytochrome-p450-20a1-cyp20a1-gene-in-the-bpa-bde-47-and-waf-exposed-copepods-tigriopus-japonicus-and-paracyclopina-nana
#15
Jeonghoon Han, Duck-Hyun Kim, Jung Soo Seo, Il-Chan Kim, David R Nelson, Jayesh Puthumana, Jae-Seong Lee
CYP20A1 is a member of the cytochrome P450 (CYP) superfamily, identified as an orphan P450 without any assigned biological function; hence, its continued status as an "orphan" gene. In order to address this shortcoming in our understanding of this superfamily, we sought to characterize the CYP20A1 gene in the copepods Tigriopus japonicus (Tj-CYP20A1) and Paracyclopina nana (Pn-CYP20A1) at their mRNA transcriptional level. We assessed the response of this gene's expression in various developmental stages and in response to treatment with bisphenol A (BPA), 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), and water accommodated fractions (WAFs) of crude oil...
January 11, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28086803/compendium-of-tcdd-mediated-transcriptomic-response-datasets-in-mammalian-model-systems
#16
Stephenie D Prokopec, Kathleen E Houlahan, Ren X Sun, John D Watson, Cindy Q Yao, Jamie Lee, Christine P'ng, Renee Pang, Alexander H Wu, Lauren C Chong, Ashley B Smith, Nicholas J Harding, Ivy D Moffat, Jere Lindén, Sanna Lensu, Allan B Okey, Raimo Pohjanvirta, Paul C Boutros
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28081574/gstp1-and-cyp2b6-genetic-polymorphisms-and-the-risk-of-bronchopulmonary-dysplasia-in-preterm-neonates
#17
Sophia Zachaki, Aggeliki Daraki, Elena Polycarpou, Chrysa Stavropoulou, Kalliopi N Manola, Stavroula Gavrili
Objectives Antioxidant response plays a key role in bronchopulmonary dysplasia (BPD) pathogenesis. The glutathione-S-tranferases pi 1 (GSTP1) and cytochrome P450 (CYP) detoxification enzymes protect cells from oxidative damage. The aim of the study was to investigate whether the A(313)G GSTP1 and G(516)T CYP2B6 inactivating polymorphisms could be associated with BPD susceptibility. Study Design To test this hypothesis, we conducted a case-control study enrolled 138 premature neonates ≤32 weeks of gestational age; of the 138, 46 developed BPD and 92 did not develop BPD...
January 12, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28078726/dissecting-the-cytochrome-p450-1a2-and-3a4-mediated-metabolism-of-aflatoxin-b1-in-ligand-and-protein-contributions
#18
Lars Olsen, Flemming S Jørgensen, Silvia Bonomo
Aflatoxin B1 (AFB1) is a chemically intriguing compound because it has several potential sites of metabolism (SOMs) while only some of them are observed experimentally. Cytochrome P450 (CYP) 3A4 and 1A2 are the major isoforms involved in its metabolism. Here, we systematically investigate reactivity and accessibility of all possible SOMs in these two CYPs to elucidate AFB1 metabolism. Density functional theory (DFT) calculations were used to determine activation energies for each possible reaction. Aliphatic hydroxylation on position 9A and 3α are energetically favored, whereas position 9 is the preferred site for epoxidation...
January 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28078076/sex-dependent-alteration-of-cardiac-cytochrome-p450-gene-expression-by-doxorubicin-in-c57bl-6-mice
#19
Marianne K O Grant, Davis M Seelig, Leslie C Sharkey, Beshay N Zordoky
BACKGROUND: There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28077318/alcohol-microbiome-life-style-influence-alcohol-and-non-alcoholic-organ-damage
#20
REVIEW
Manuela G Neuman, Samuel W French, Samir Zakhari, Stefen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, onJune 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealedthe basic aspects of alcohol metabolism that may be responsible for the development of liver diseaseas well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
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