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https://www.readbyqxmd.com/read/28436560/development-of-a-high-throughput-genotoxicity-assay-using-umu-test-strains-expressing-human-cytochrome-p450s-and-nadph-p450-reductase-and-bacterial-o-acetyltransferase
#1
Hisako Hori, Daisuke Hirata, Wataru Fujii, Yoshimitsu Oda
Umu test is one of the in vitro genotoxicity test that has been used widely. It was developed as a high-throughput test system using the 96-well microplate. We have previously constructed new umu test strains for the evaluation of genotoxicity of procarcinogenic metabolic products formed by cytochrome P450 (CYP) enzymes. In this study, a highly sensitive high-throughput genotoxicity test was developed using four umu test strains (OY1002/1A1, OY1002/1B1, OY1002/1A2, and OY1002/3A4) that express human CYPs and NADPH-P450 reductase...
April 24, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28413083/a-novel-nuclear-xenobiotic-receptors-ahr-pxr-car-mediated-mechanism-of-dehp-induced-cerebellar-toxicity-in-quails-coturnix-japonica-via-disrupting-cyp-enzyme-system-homeostasis
#2
Zheng-Hai Du, Jun Xia, Xiao-Chen Sun, Xue-Nan Li, Cong Zhang, Hua-Shan Zhao, Shi-Yong Zhu, Jin-Long Li
Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neurobehavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails...
April 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28410957/fetal-alpha-5-reductase-val89leu-mutation-is-associated-with-late-miscarriage
#3
Beatriz Pérez-Nevot, Jose-Luis Royo, Miriam Cortés, Ana M Lendínez, Arturo Reyes-Palomares, Ana-José Jiménez, Maximiliano Ruiz-Galdón, Armando Reyes-Engel
The present study was undertaken to determine the role of different polymorphisms affecting the testosterone/oestrogen pathway in miscarriage. Alpha 5-reductase (SRD5A2) rs523349 and rs9282858, cytochrome P450 aromatase (CYP19A1) rs4646, rs10046 and rs2236722 and oestrogen receptor (ESR1) rs9340799, rs2234693 and rs6932902 polymorphisms were selected. The case group consisted of 94 samples of formalin-fixed and paraffin-embedded fetal tissue from a miscarriage at ≤24 weeks. The control group comprised a population of 331 young healthy subjects...
March 21, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28410952/molecular-cloning-and-functional-characterization-of-multiple-nadph-cytochrome-p450-reductases-from-andrographis-paniculata
#4
Huixin Lin, Jian Wang, Mengdie Qi, Juan Guo, Qixian Rong, Jinfu Tang, Yisheng Wu, Xiaojing Ma, Luqi Huang
Andrographis paniculata (Burm.f.) Wall. ex Nees is widely used as medicinal herb in Southern and Southeastern Asia and andrographolide is its main medicinal constituent. Based on the structure of andrographolide, it has been proposed that cytochrome P450 enzymes play vital roles on its biosynthesis. NADPH:cytochrome P450 reductase (CPR) is the most important redox partner of multiple P450s. In this study, three CPRs were identified in the genomic data of A. paniculata (namely ApCPR1, ApCPR2, and ApCPR3), and their coding regions were cloned...
April 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28388834/epsilonproteobacterial-hydroxylamine-oxidoreductase-%C3%AE%C2%B5hao-characterization-of-a-missing-link-in-the-multihaem-cytochrome-c-family
#5
Doreen Haase, Bianca Hermann, Oliver Einsle, Jorg Simon
Members of the multihaem cytochrome c (MCC) family such as pentahaem cytochrome c nitrite reductase (NrfA) or octahaem hydroxylamine oxidoreductase (Hao) are involved in various microbial respiratory electron transport chains. Some members of the Hao subfamily, here called εHao proteins, have been predicted from the genomes of nitrate/nitrite-ammonifying bacteria that usually lack NrfA. Here, εHao proteins from the host-associated Epsilonproteobacteria Campylobacter fetus and Campylobacter curvus and the deep-sea hydrothermal vent bacteria Caminibacter mediatlanticus and Nautilia profundicola were purified as εHao-maltose binding protein fusions produced in Wolinella succinogenes...
April 7, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28382877/common-genetic-variants-are-associated-with-lower-serum-25-hydroxyvitamin-d-concentrations-across-the-year-among-children-at-northern-latitudes
#6
Rikke A Petersen, Lesli H Larsen, Camilla T Damsgaard, Louise B Sørensen, Mads F Hjorth, Rikke Andersen, Inge Tetens, Henrik Krarup, Christian Ritz, Arne Astrup, Kim F Michaelsen, Christian Mølgaard
In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped...
April 6, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28377716/human-cytochrome-p450-3a4-as-a-biocatalyst-effects-of-the-engineered-linker-in-modulation-of-coupling-efficiency-in-3a4-bmr-chimeras
#7
Danilo Degregorio, Serena D'Avino, Silvia Castrignanò, Giovanna Di Nardo, Sheila J Sadeghi, Gianluca Catucci, Gianfranco Gilardi
Human liver cytochrome P450 3A4 is the main enzyme involved in drug metabolism. This makes it an attractive target for biocatalytic applications, such as the synthesis of pharmaceuticals and drug metabolites. However, its poor solubility, stability and low coupling have limited its application in the biotechnological context. We previously demonstrated that the solubility of P450 3A4 can be increased by creating fusion proteins between the reductase from Bacillus megaterium BM3 (BMR) and the N-terminally modified P450 3A4 (3A4-BMR)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28373679/the-function-of-two-p450s-cyp9m10-and-cyp6aa7-in-the-permethrin-resistance-of-culex-quinquefasciatus
#8
Youhui Gong, Ting Li, Yucheng Feng, Nannan Liu
Cytochrome P450 monooxygenases play a critical role in insecticide resistance by allowing resistant insects to metabolize insecticides. Previous studies revealed that two P450 genes, CYP9M10 and CYP6AA7, are not only up-regulated but also induced in resistant Culex mosquitoes. In this study, CYP9M10 and CYP6AA7 were separately co-expressed with cytochrome P450 reductase (CPR) in insect Spodoptera frugiperda (Sf9) cells using a baculovirus-mediated expression system and the enzymatic activity and metabolic ability of CYP9M10/CPR and CYP6AA7/CPR to permethrin and its metabolites, including 3-phenoxybenzoic alcohol (PBOH) and 3-phenoxybenzaldehyde (PBCHO), characterized...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361965/transcriptomics-and-proteomic-studies-reveal-acaricidal-mechanism-of-octadecanoic-acid-3-4-tetrahydrofuran-diester-against-sarcoptes-scabiei-var-cuniculi
#9
Xu Song, Zhenzhen Chen, Renyong Jia, Mei Cao, Yuanfeng Zou, Lixia Li, Xiaoxia Liang, Lizi Yin, Changliang He, Guizhou Yue, Zhongqiong Yin
In our previous study, a new compound, octadecanoic acid-3, 4-tetrahydrofuran diester, possessing potent acaricidal activity was obtained from neem oil. This study performed RNA-seq transcriptomics and iTRAQ proteomics to uncover the acaricidal mechanism of the compound against Sarcoptes scabiei var. cuniculi. The results of transcriptomics indicated that after treatment with octadecanoic acid-3, 4-tetrahydrofuran diester, genes related to "Energy metabolism" were significantly up-/down-regulated, including citrate cycle, oxidative phosphorylation pathway and fatty acid metabolism...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28347139/single-protein-tracking-reveals-that-nadph-mediates-the-insertion-of-cytochrome-p450-reductase-into-a-biomimetic-of-the-endoplasmic-reticulum
#10
Carlo Barnaba, Michael J Martinez, Evan Taylor, Adam O Barden, James A Brozik
Cytochrome P450 reductase (CPR) is the redox partner for most human cytochrome P450 enzymes. It is also believed that CPR is an integral membrane protein exclusively. Herein, we report that, contrary to this belief, CPR can exist as a peripheral membrane protein in the absence of NADPH and will transition to an integral membrane protein in the presence of stoichiometric amounts of NADPH or greater. All experiments were performed in a solid-supported cushioned lipid bilayer that closely matched the chemical composition of the human endoplasmic reticulum and served as an ER biomimetic...
April 6, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28346709/synthetic-%C3%AE-nitrostyrene-derivative-cyt-rx20-as-inhibitor-of-oral-cancer-cell-proliferation-and-tumor-growth-through-glutathione-suppression-and-reactive-oxygen-species-induction
#11
Yen-Yun Wang, Yuk-Kwan Chen, Ya-Ling Hsu, Wen-Chin Chiu, Chun-Hao Tsai, Stephen Chu-Sung Hu, Pei-Wen Hsieh, Shyng-Shiou F Yuan
BACKGROUND: The β-nitrostyrene family possesses anticancer properties. In this study, β-nitrostyrene derivative CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene) was synthesized and investigated its anticancer activity in oral cancer. METHODS: Anticancer activity of CYT-Rx20 and the underlying mechanisms were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, fluorescence-activated cell sorter analysis, annexin V staining, comet assay, glutathione (GSH)/glutathione disulfide (GSSG) ratio, immunoblotting, soft agar assay, nude mice xenograft study, and immunohistochemistry...
March 27, 2017: Head & Neck
https://www.readbyqxmd.com/read/28335548/study-of-different-variants-of-mo-enzyme-crarc-and-the-interaction-with-its-partners-crcytb5-r-and-crcytb5-1
#12
Alejandro Chamizo-Ampudia, Aurora Galvan, Emilio Fernandez, Angel Llamas
The mARC (mitochondrial Amidoxime Reducing Component) proteins are recently discovered molybdenum (Mo) Cofactor containing enzymes. They are involved in the reduction of several N-hydroxylated compounds (NHC) and nitrite. Some NHC are prodrugs containing an amidoxime structure or mutagens such as 6-hydroxylaminopurine (HAP). We have studied this protein in the green alga Chlamydomonas reinhardtii (crARC). Interestingly, all the ARC proteins need the reducing power supplied by other proteins. It is known that crARC requires a cytochrome b₅ (crCytb5-1) and a cytochrome b₅ reductase (crCytb5-R) that form an electron transport chain from NADH to the substrates...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28333392/the-biosynthesis-of-nitrous-oxide-in-the-green-alga-chlamydomonas-reinhardtii
#13
Maxence Plouviez, David Wheeler, Andy Shilton, Michael A Packer, Patricia A McLenachan, Emanuel Sanz-Luque, Francisco Ocaña-Calahorro, Emilio Fernández, Benoit Guieysse
Over the last decades, several studies have reported emissions of nitrous oxide (N2 O) from microalgae cultures and aquatic ecosystems characterized by a high level of algal activity (e.g. eutrophic lakes). As N2 O is a potent greenhouse gas (GHG) and an ozone depleting pollutant, these findings suggest that large scale microalgae cultivation (and possibly, natural eutrophic ecosystems) could have significant environmental impacts. Using the model unicellular microalga Chlamydomonas reinhardtii, this study was conducted to investigate the molecular basis of microalgal N2 O synthesis...
March 23, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28332314/the-mitochondrial-hinge-protein-uqcrh-is-a-novel-prognostic-factor-for-hepatocellular-carcinoma
#14
Eun-Ran Park, Sang-Bum Kim, Jee-San Lee, Yang-Hyun Kim, Dong-Hyoung Lee, Eung-Ho Cho, Sun-Hoo Park, Chul Ju Han, Bu-Yeo Kim, Dong Wook Choi, Young Do Yoo, Ami Yu, Jae Won Lee, Ja June Jang, Young Nyun Park, Kyung-Suk Suh, Kee-Ho Lee
Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28317859/physiological-and-transcriptional-approaches-reveal-connection-between-nitrogen-and-manganese-cycles-in-shewanella-algae-c6g3
#15
Axel Aigle, Patricia Bonin, Chantal Iobbi-Nivol, Vincent Méjean, Valérie Michotey
To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28306139/the-tir-bb-loop-mimetic-as-1-prevents-nonalcoholic-steatohepatitis-and-hepatic-insulin-resistance-by-inhibiting-nlrp3-asc-inflammasome-activation
#16
Xiaolu Wang, Yun Gao, Juan Song, Chao Tang, Man Wang, Linli Que, Li Liu, Guoqing Zhu, Qi Chen, Yong Yao, Yong Xu, Jiantao Li, Yuehua Li
BACKGROUND AND PURPOSE: Non-alcoholic steatohepatitis (NASH) is characterized by excessive intracellular lipid accumulation, inflammation and hepatic insulin resistance. Considering the rising prevalence of NASH worldwide, it is urgent to find novel interventional approaches. The pro-inflammatory cytokine IL-1β, generated and released from the Kupffer cells, is considered to be an initiating event in NASH. AS-1, a synthetic low-molecule mimetic to myeloid differentiation primary response gene 88 (MyD88), has been reported to disrupt the IL-1R-MyD88 interaction...
March 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28294491/an-efficient-chemoenzymatic-synthesis-of-dihydroartemisinic-aldehyde
#17
Melodi Demiray, Xiaoping Tang, Thomas Wirth, Juan A Faraldos, Rudolf K Allemann
Artemisinin from the plant Artemisia annua is the most potent pharmaceutical for the treatment of malaria. In the plant, the sesquiterpene cyclase amorphadiene synthase, a cytochrome-dependent CYP450, and an aldehyde reductase convert farnesyl diphosphate (FDP) into dihydroartemisinic aldehyde (DHAAl), which is a key intermediate in the biosynthesis of artemisinin and a semisynthetic precursor for its chemical synthesis. Here, we report a chemoenzymatic process that is able to deliver DHAAl using only the sesquiterpene synthase from a carefully designed hydroxylated FDP derivative...
April 3, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28286729/a-novel-cytochrome-p450-cyp3201b1-is-involved-in-r-mandelonitrile-biosynthesis-in-a-cyanogenic-millipede
#18
Takuya Yamaguchi, Yasumasa Kuwahara, Yasuhisa Asano
Specialized arthropods and more than 2500 plant species biosynthesize hydroxynitriles and release hydrogen cyanide as a defensive mechanism. The millipede Chamberlinius hualienensis accumulates (R)-mandelonitrile as a cyanide precursor. Although biosynthesis of hydroxynitriles in cyanogenic plants and in an insect are extensively studied, (R)-mandelonitrile biosynthesis in cyanogenic millipedes has remained unclear. In this study, we identified the biosynthetic precursors of (R)-mandelonitrile and an enzyme involved in (R)-mandelonitrile biosynthesis...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28285895/transcriptomic-analysis-of-basidiocarp-development-in-ustilago-maydis-dc-cda
#19
C G León-Ramírez, J L Cabrera-Ponce, D Martínez-Soto, A Sánchez-Arreguin, E T Aréchiga-Carvajal, J Ruiz-Herrera
Previously, we demonstrated that when Ustilago maydis (DC) Cda., a phytopathogenic basidiomycete and the causal agent of corn smut, is grown in the vicinity of maize embryogenic calli in a medium supplemented with the herbicide Dicamba, it developed gastroid-like basidiocarps. To elucidate the molecular mechanisms involved in the basidiocarp development by the fungus, we proceeded to analyze the transcriptome of the process, identifying a total of 2002 and 1064 differentially expressed genes at two developmental stages, young and mature basidiocarps, respectively...
March 7, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28285348/n-adamantyl-4-methylthiazol-2-amine-attenuates-glutamate-induced-oxidative-stress-and-inflammation-in-the-brain
#20
Seung-Ju Yang, Eun-A Kim, Min-Jun Chang, Jiae Kim, Jung-Min Na, Soo Young Choi, Sung-Woo Cho
In this study, we explored the possible mechanisms underlying the neuroprotective and anti-oxidative effects of N-adamantyl-4-methylthiazol-2-amine (KHG26693) against in vivo glutamate-induced toxicity in the rat cerebral cortex. Our results showed that pretreatment with KHG26693 significantly attenuated glutamate-induced elevation of lipid peroxidation, tumor necrosis factor-α, interferon gamma, IFN-γ, interleukin-1β, nitric oxide, reactive oxygen species, NADPH oxidase, caspase-3, calpain activity, and Bax...
March 11, 2017: Neurotoxicity Research
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