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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/28062520/tsdc-a-unique-lipoprotein-from-wolinella-succinogenes-that-enhances-tetrathionate-reductase-activity-of-tsda
#3
Julia M Kurth, Anja Schuster, Waldemar Seel, Stefanie Herresthal, Jörg Simon, Christiane Dahl
The diheme cytochromes c of the widespread TsdA family are bifunctional thiosulfate dehydrogenase/tetrathionate reductases. Here, biochemical information was collected about TsdA from the Epsilonproteobacterium Wolinella succinogenes (WsTsdA). The situation in W. succinogenes is unique since TsdA is closely associated with the unprecedented lipoprotein TsdC encoded immediately downstream of tsdA in the same direction of transcription. WsTsdA purified from Escherichia coli catalyzed both thiosulfate oxidation and tetrathionate reduction...
January 6, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28043840/characterization-of-cytochrome-p450-cyp109e1-from-bacillus-megaterium-as-a-novel-vitamin-d3-hydroxylase
#4
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/28043034/oxidative-stress-biomarkers-cholinesterase-activity-and-biotransformation-enzymes-in-the-liver-of-dice-snake-natrix-tessellata-laurenti-during-pre-hibernation-and-post-hibernation-a-possible-correlation-with-heavy-metals-in-the-environment
#5
Jelena Gavrić, Marko Anđelković, Ljiljana Tomović, Marko Prokić, Svetlana Despotović, Branka Gavrilović, Tijana Radovanović, Slavica Borković-Mitić, Slađan Pavlović, Zorica Saičić
We investigated in the liver of dice snakes during pre- and post-hibernation changes in the following antioxidant parameters: total, manganese and copper zinc containing superoxide dismutases (Tot SOD, MnSOD, CuZn SOD, respectively), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the concentrations of total glutathione (GSH) and sulfhydryl groups (-SH). In addition, we examined the expression of phase I biotransformation enzyme cytochrome P4501A (CYP1A) and the activity of phase II biotransformation enzyme glutathioneS-transferase (GST), the level of lipid peroxidation (by measuring the thiobarbituric acid-reactive substances (TBARS)), cholinesterase activity (ChE) and metallothionein expression (MT)...
December 30, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28040652/enhancing-saccharomyces-cerevisiae-reactive-oxygen-species-and-ethanol-stress-tolerance-for-high-level-production-of-protopanoxadiol
#6
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...
March 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28032259/role-of-the-nad-p-h-quinone-oxidoreductase-nqr-and-the-cytochrome-b-air12-in-controlling-superoxide-generation-at-the-plasma-membrane
#7
Catherine Biniek, Eiri Heyno, Jerzy Kruk, Francesca Sparla, Paolo Trost, Anja Krieger-Liszkay
The quinone reductase NQR and the b-type cytochrome AIR12 of the plasma membrane are important for the control of reactive oxygen species in the apoplast. AIR12 and NQR are two proteins attached to the plant plasma membrane which may be important for generating and controlling levels of reactive oxygen species in the apoplast. AIR12 (Auxin Induced in Root culture) is a single gene of Arabidopsis that codes for a mono-heme cytochrome b. The NADPH quinone oxidoreductase NQR is a two-electron-transferring flavoenzyme that contributes to the generation of O 2(•-) in isolated plasma membranes...
December 28, 2016: Planta
https://www.readbyqxmd.com/read/28027877/hydrogen-sulfide-may-attenuate-methylmercury-induced-neurotoxicity-via-mitochondrial-preservation
#8
Junyan Han, Xuelian Yang, Xuehua Chen, Zhiqiang Li, Ming Fang, Bing Bai, Dehong Tan
Hydrogen sulfide (H2S) is a protective molecule and a novel gaseous mediator. Here we explored whether H2S donor (NaHS) could attenuate methylmercury (MeHg)-induced neurotoxicity in rats. The adult rats were randomly divided into four groups, i.e., control, NaHS, MeHg, and NaHS + MeHg groups. Rats of the NaHS + MeHg group were intraperitoneally (i.p) injected with 5.6 mg/kg/d of NaHS together with 5 μg/kg/d of MeHg. Rats of the MeHg group and NaHS group were injected with 5 μg/kg/d of MeHg and 5.6 mg/kg/d of NaHS, respectively...
December 24, 2016: Chemico-biological Interactions
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
#9
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/28007593/down-regulation-of-msrb3-induces-cancer-cell-apoptosis-through-reactive-oxygen-species-production-and-intrinsic-mitochondrial-pathway-activation
#10
Geun-Hee Kwak, Tae-Hyoung Kim, Hwa-Young Kim
Methionine sulfoxide reductase B3 (MsrB3) is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues and has an antioxidant function. We have previously shown that depletion of MsrB3 suppresses the proliferation of normal mammalian cells by arresting cell cycle. In this study, we report the crucial role of MsrB3 in cancer cell death. Deficiency of MsrB3 induced cancer cell death, while MsrB3 overexpression stimulated cancer cell proliferation. MsrB3 depletion resulted in apoptotic cancer cell death through the activation of the intrinsic mitochondrial pathway...
December 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28007448/bioreductively-activatable-prodrug-conjugates-of-phenstatin-designed-to-target-tumor-hypoxia
#11
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...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27994808/effects-of-benzo-e-pyrene-on-reactive-oxygen-nitrogen-species-and-inflammatory-cytokines-induction-in-human-rpe-cells-and-attenuation-by-mitochondrial-involved-mechanism
#12
M Fernanda Estrago-Franco, M Tarek Moustafa, Mohammad Riazi-Esfahani, Ashish U Sapkal, Rhina Piche-Lopez, A Jayaprakash Patil, Ashish Sharma, Payam Falatoonzadeh, Marilyn Chwa, Georgia Luczy-Bachman, Baruch D Kuppermann, M Cristina Kenney
PURPOSE: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay...
October 2016: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/27992998/asymmetric-binding-and-metabolism-of-polyunsaturated-fatty-acids-pufas-by-cyp2j2-epoxygenase
#13
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
#14
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/27959492/can-reduction-of-no-to-n2o-in-cytochrome-c-dependent-nitric-oxide-reductase-proceed-through-a-trans-mechanism
#15
Margareta R A Blomberg
As part of microbial denitrification, NO is reduced to N2O in the membrane bound enzyme nitric oxide reductase, NOR. The N-N coupling occurs in the diiron binuclear active site, BNC, and different mechanisms for this reaction step have been suggested. Computational studies have supported a so-called cis:b3-mechanism, in which the hyponitrite product of the reductive N-N bond formation coordinates with one nitrogen to the heme iron and with both oxygens to the non-heme iron in the BNC. In contrast, experimental results have been interpreted to support a so-called trans-mechanism, in which the hyponitrite intermediate coordinates with one nitrogen atom to each of the two iron ions...
December 21, 2016: Biochemistry
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
#16
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
#17
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
#18
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
#19
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
#20
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
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