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cytochrome P450 reductase

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https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#1
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28065637/the-steroid-metabolite-16-%C3%AE-oh-androstenedione-generated-by-cyp21a2-serves-as-a-substrate-for-cyp19a1
#2
J Neunzig, M Milhim, L Schiffer, Y Khatri, J Zapp, A Sánchez-Guijo, M F Hartmann, S A Wudy, R Bernhardt
The 21-hydroxylase (CYP21A2) is a steroidogenic enzyme crucial for the synthesis of mineralo- and glucocorticoids. It is described to convert progesterone as well as 17-OH-progesterone, through a hydroxylation at position C21, into 11-deoxycorticosterone (DOC) and 11-deoxycortisol (RSS), respectively. In this study we unraveled CYP21A2 to have a broader steroid substrate spectrum than assumed. Utilizing a reconstituted in vitro system, consisting of purified human CYP21A2 and human cytochrome P450 reductase (CPR) we demonstrated that CYP21A2 is capable to metabolize DOC, RSS, androstenedione (A4) and testosterone (T)...
January 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28043840/characterization-of-cytochrome-p450-cyp109e1-from-bacillus-megaterium-as-a-novel-vitamin-d3-hydroxylase
#3
Ammar Abdulmughni, Ilona K Jóźwik, Natalia Putkaradze, Elisa Brill, Josef Zapp, Andy-Mark W H Thunnissen, Frank Hannemann, Rita Bernhardt
In this study the ability of CYP109E1 from Bacillus megaterium to metabolize vitamin D3 (VD3) was investigated. In an in vitro system using bovine adrenodoxin reductase (AdR) and adrenodoxin (Adx4-108), VD3 was converted by CYP109E1 into several products. Furthermore, a whole-cell system in B. megaterium MS941 was established. The new system showed a conversion of 95% after 24h. By NMR analysis it was found that CYP109E1 catalyzes hydroxylation of VD3 at carbons C-24 and C-25, resulting in the formation of 24(S)-hydroxyvitamin D3 (24S(OH)VD3), 25-hydroxyvitamin D3 (25(OH)VD3) and 24S,25-dihydroxyvitamin D3 (24S,25(OH)2VD3)...
December 30, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/28040652/enhancing-saccharomyces-cerevisiae-reactive-oxygen-species-and-ethanol-stress-tolerance-for-high-level-production-of-protopanoxadiol
#4
Fanglong Zhao, Yanhui Du, Peng Bai, Jingjing Liu, Wenyu Lu, Yingjin Yuan
Protopanaxadiol (PPD) is an active compound in Panax ginseng. Recently, an optimized PPD synthesis pathway contained a ROS releasing step (a P450-type PPD synthase, PPDS) was introduced into Saccharomyces cerevisiae. Here reported a synergistic effect of PPDS-CPR (CPR, cytochrome P450 reductase) uncoupling and ethanol stress on ROS releasing, which reduced cells viability. To build a robust strain, a cell wall integrity associated gene SSD1 was high-expressed to improve ethanol tolerance, and ROS level decreased for 24...
December 22, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/28027470/performance-of-a-novel-atrazine-induced-cerebellar-toxicity-in-quail-coturnix-c-coturnix-activating-pxr-car-pathway-responses-and-disrupting-cytochrome-p450-homeostasis
#5
Jun Xia, Lei Qin, Zheng-Hai Du, Jia Lin, Xue-Nan Li, Jin-Long Li
Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum...
December 18, 2016: Chemosphere
https://www.readbyqxmd.com/read/28007448/bioreductively-activatable-prodrug-conjugates-of-phenstatin-designed-to-target-tumor-hypoxia
#6
Blake A Winn, Zhe Shi, Graham J Carlson, Yifan Wang, Benson L Nguyen, Evan M Kelly, R David Ross, Ernest Hamel, David J Chaplin, Mary L Trawick, Kevin G Pinney
A variety of solid tumor cancers contain significant regions of hypoxia, which provide unique challenges for targeting by potent anticancer agents. Bioreductively activatable prodrug conjugates (BAPCs) represent a promising strategy for therapeutic intervention. BAPCs are designed to be biologically inert until they come into contact with low oxygen tension, at which point reductase enzyme mediated cleavage releases the parent anticancer agent in a tumor-specific manner. Phenstatin is a potent inhibitor of tubulin polymerization, mimicking the chemical structure and biological activity of the natural product combretastatin A-4...
December 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27992998/asymmetric-binding-and-metabolism-of-polyunsaturated-fatty-acids-pufas-by-cyp2j2-epoxygenase
#7
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/27983606/functional-analysis-of-the-fusarielin-biosynthetic-gene-cluster
#8
Aida Droce, Wagma Saei, Simon Hartung Jørgensen, Reinhard Wimmer, Henriette Giese, Rasmus Dam Wollenberg, Teis Esben Sondergaard, Jens Laurids Sørensen
Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually in a Fusarium graminearum strain overexpressing the local transcription factor. The results suggest that a trans-acting enoyl reductase (FSL5) assists the polyketide synthase FSL1 in biosynthesis of a polyketide product, which is released by hydrolysis by a trans-acting thioesterase (FSL2)...
December 13, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27940401/dna-damage-induced-by-nadph-cytochrome-p450-reductase-activated-idarubicin-in-sensitive-and-multidrug-resistant-mcf7-breast-cancer-cells
#9
Wojciech Żwierełło, Agnieszka Maruszewska, Robert Nowak, Dorota Kostrzewa-Nowak, Jolanta Tarasiuk
BACKGROUND: Idarubicin (IDA) is one of clinically important anticancer drugs belonging to the anthracycline antibiotic family. The aim of this study was to examine DNA damage induced by NADPH cytochrome P450 reductase (CPR)-activated IDA in human sensitive MCF7 and multidrug resistant MCF7/DOX500 (overexpressing P-gp) breast adenocarcinoma cells. METHODS: The evaluation of DNA fragmentation caused by single strand breaks (SSB) and double strand breaks (DSB) was performed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) test...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27910907/micrornas-modulate-adaption-to-multiple-abiotic-stresses-in-chlamydomonas-reinhardtii
#10
Xiang Gao, Fengge Zhang, Jinlu Hu, Wenkai Cai, Ge Shan, Dongsheng Dai, Kaiyao Huang, Gaohong Wang
MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899849/statin-therapy-review-of-safety-and-potential-side-effects
#11
REVIEW
Satish Ramkumar, Ajay Raghunath, Sudhakshini Raghunath
BACKGROUND: Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins...
November 2016: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/27890531/short-term-effects-of-diabetes-on-neurosteroidogenesis-in-the-rat-hippocampus
#12
Simone Romano, Nico Mitro, Silvia Diviccaro, Roberto Spezzano, Matteo Audano, Luis Miguel Garcia-Segura, Donatella Caruso, Roberto Cosimo Melcangi
Diabetes may induce neurophysiological and structural changes in the central nervous system (i.e., diabetic encephalopathy). We here explored whether the levels of neuroactive steroids (i.e., neuroprotective agents) in the hippocampus may be altered by short-term diabetes (i.e., one month). To this aim, by liquid chromatography-tandem mass spectrometry we observed that in the experimental model of the rat raised diabetic by streptozotocin injection, one month of pathology induced changes in the levels of several neuroactive steroids, such as pregnenolone, progesterone and its metabolites (i...
November 23, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27888364/in-vitro-reconstitution-of-the-cyclosporine-specific-p450-hydroxylases-using-heterologous-redox-partner-proteins
#13
Yue Sun, Li Ma, Dongfei Han, Lei Du, Fengxia Qi, Wei Zhang, Jingran Sun, Shan Huang, Eung-Soo Kim, Shengying Li
The cytochrome P450 enzymes (CYPs) CYP-sb21 from Sebekia benihana and CYP-pa1 from Pseudonocardia autotrophica are able to hydroxylate the immunosuppressant cyclosporin A (CsA) in a regioselective manner, giving rise to the production of two hair-stimulating agents (with dramatically attenuated immunosuppressant activity), γ-hydroxy-N-methyl-L-Leu4-CsA (CsA-4-OH) and γ-hydroxy-N-methyl-L-Leu9-CsA (CsA-9-OH). Recently, the in vitro activity of CYP-sb21 was identified using several surrogate redox partner proteins...
November 25, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27879469/frequency-of-common-vkorc1-polymorphisms-and-their-impact-on-warfarin-dose-requirement-in-pakistani-population
#14
Aisha Qayyum, Muzammil Hasan Najmi, Qaisar Mansoor, Muhammad Irfan, Abdul Khaliq Naveed, Andleeb Hanif, Ali Raza Kazmi, Muhammad Ismail
Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations...
November 21, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27872699/the-effects-of-fenvalerate-on-hepatic-and-cerebral-xenobiotic-metabolizing-enzymes-in-selenium-and-or-iodine-deficient-rats
#15
Aydan Caglayan, Belma Kocer-Gumusel, Pinar Erkekoglu, Filiz Hincal
OBJECTIVES: Particularly in developing countries, selenium and/or iodine deficiencies are encountered and use of pesticides in agriculture are not well-controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has applications against a wide range of pests. This study was designed to evaluate the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme activities in the presence of iodine and/or selenium deficiency on a rat model. MATERIALS AND METHODS: Iodine and/or selenium deficiency was induced by feeding three-week-old Wistar rats with a diet containing <0...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27866976/protective-effect-of-rosiglitazone-against-acetaminophen-induced-acute-liver-injury-is-associated-with-down-regulation-of-hepatic-nadph-oxidases
#16
Jun-Xian Wang, Cheng Zhang, Lin Fu, Da-Gang Zhang, Bi-Wei Wang, Zhi-Hui Zhang, Yuan-Hua Chen, Yan Lu, Xi Chen, De-Xiang Xu
The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. The aim of the present study was to investigate the effects of rosiglitazone (RSG), a synthetic PPAR-γ agonist, on acetaminophen (APAP)-induced acute liver injury. Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment alleviated APAP-induced acute liver injury...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27863990/cytochrome-p450-enzymes-but-not-nadph-oxidases-are-the-source-of-the-nadph-dependent-lucigenin-chemiluminescence-in-membrane-assays
#17
Flávia Rezende, Kim-Kristin Prior, Oliver Löwe, Ilka Wittig, Valentina Strecker, Franziska Moll, Valeska Helfinger, Frank Schnütgen, Nina Kurrle, Frank Wempe, Maria Walter, Sven Zukunft, Bert Luck, Ingrid Fleming, Norbert Weissmann, Ralf P Brandes, Katrin Schröder
: Measuring NADPH oxidase (Nox)-derived reactive oxygen species (ROS) in living tissues and cells is a constant challenge. All probes available display limitations regarding sensitivity, specificity or demand highly specialized detection techniques. In search for a presumably easy, versatile, sensitive and specific technique, numerous studies have used NADPH-stimulated assays in membrane fractions which have been suggested to reflect Nox activity. However, we previously found an unaltered activity with these assays in triple Nox knockout mouse (Nox1-Nox2-Nox4(-/-)) tissue and cells compared to wild type...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27825803/protective-effects-of-dieckol-on-n-nitrosodiethylamine-induced-hepatocarcinogenesis-in-rats
#18
Velayutham Sadeeshkumar, Arul Duraikannu, Samuthrapandian Ravichandran, Wilson Sylvester Fredrick, Ramar Sivaperumal, Paulrasu Kodisundaram
Dieckol (DEK) is a naturally occuring phlorotannins found in marine brown algae Ecklonia cava which is attributed with various pharmacological properties. This study was aimed to investigate the protective role of DEK on N-Nitrosdiethylamine (NDEA) induced rat hepatocarcinogenesis. In this investigation 0.01% NDEA in drinking water for 15 weeks to induce hepatocellular carcinoma (HCC). DEK was administered orally (10, 20 and 40mg/kg body weight) for 15 weeks with 0.01% NDEA through drinking water. Hepatocarcinogesis was measured by the increased activities of serum liver marker enzymes namely aspartate trasaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), α-fetoprotein (AFP) and total bilirubin along with increased elevation of cytochrome p450, lipid peroxidation markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP), protein carbonyl content (PCC) and conjugated dienes (CD)...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27815364/predictors-of-variation-in-cyp2a6-mrna-protein-and-enzyme-activity-in-a-human-liver-bank-influence-of-genetic-and-nongenetic-factors
#19
Julie-Anne Tanner, Bhagwat Prasad, Katrina G Claw, Patricia Stapleton, Amarjit Chaudhry, Erin G Schuetz, Kenneth E Thummel, Rachel F Tyndale
Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Smokers vary widely in their rate of inactivation and clearance of nicotine, altering numerous smoking phenotypes. We aimed to characterize independent and shared impact of genetic and nongenetic sources of variation in CYP2A6 mRNA, protein, and enzyme activity in a human liver bank (n = 360). For the assessment of genetic factors, we quantified levels of CYP2A6, cytochrome P450 oxidoreductase (POR), and aldo-keto reductase 1D1 (AKR1D1) mRNA, and CYP2A6 and POR proteins...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27814979/improving-the-activity-of-surface-displayed-cytochrome-p450-enzymes-by-optimizing-the-outer-membrane-linker
#20
Paul Quehl, Jan Schüürmann, Joel Hollender, Joachim Jose
Anchorage of recombinant proteins onto the outer membrane of gram-negative bacteria is an attractive solution for protein library screening and whole cell biocatalysis if a membrane environment is required or mass transfer into the cell is limiting. Autotransporters have been successfully applied for surface display of various heterologous proteins. Still, many underlying parameters for achieving active enzymes are not known. Here, we systematically tested different linkers between passenger and the membrane embedded β-barrel of the autotransporter...
January 2017: Biochimica et Biophysica Acta
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