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cytochrom p450

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https://www.readbyqxmd.com/read/28822867/de-novo-assembly-and-characterization-of-seabass-lateolabrax-japonicus-transcriptome-and-expression-of-hepatic-genes-following-different-dietary-phosphorus-calcium-levels
#1
Kang-Le Lu, Zhong-Li Ji, Samad Rahimnejad, Chun-Xiao Zhang, Ling Wang, Kai Song
Fish farming seriously influences the aquatic environment because most dietary phosphorus (P) is excreted in the effluent. To increase the P utilization in fish, molecular techniques should be explored given the remarkable development of these techniques. Thus, to identify the candidate genes related to P utilization and molecular alterations following administration of a P-deficient diet in seabass Lateolabrax japonicus, we assessed the de novo pituitary, gill, intestine, liver, kidney, scales and vertebra transcriptomes, and we compared the expression of hepatic genes with three diets varying in P and Ca levels: diet I (0...
August 9, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28822812/determinants-of-thermostability-in-the-cytochrome-p450-fold
#2
REVIEW
Kurt L Harris, Raine E S Thomson, Silja J Strohmaier, Yosephine Gumulya, Elizabeth M J Gillam
Cytochromes P450 are found throughout the biosphere in a wide range of environments, serving a multitude of physiological functions. The ubiquity of the P450 fold suggests that it has been co-opted by evolution many times, and likely presents a useful compromise between structural stability and conformational flexibility. The diversity of substrates metabolized and reactions catalyzed by P450s makes them attractive starting materials for use as biocatalysts of commercially useful reactions. However, process conditions impose different requirements on enzymes to those in which they have evolved naturally...
August 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28822783/the-expression-induction-and-pharmacological-activity-of-cyp1a2-are-post-transcriptionally-regulated-by-microrna-hsa-mir-132-5p
#3
Yinting Chen, Linjuan Zeng, Yong Wang, William H Tolleson, Bridgett Knox, Si Chen, Zhen Ren, Lei Guo, Nan Mei, Feng Qian, Kaihong Huang, David Liu, Weida Tong, Dianke Yu, Baitang Ning
Cytochrome P450 1A2 (CYP1A2) is one of the most abundant and important drug metabolizing enzymes in human liver. However, little is known about the post-transcriptional regulation of CYP1A2, especially the mechanisms involving microRNAs (miRNAs). This study applied a systematic approach to investigate the post-transcriptional regulation of CYP1A2 by miRNAs. Candidate miRNAs targeting the 3'-untranslated region (3'-UTR) of CYP1A2 were screened in silico, resulting in the selection of sixty-two potential miRNAs for further analysis...
August 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28821467/in-vitro-characterization-of-cyp102g4-from-streptomyces-cattleya-a-self-sufficient-p450-naturally-producing-indigo
#4
Joonwon Kim, Pyung-Gang Lee, Eun-Ok Jung, Byung-Gee Kim
Self-sufficient CYP102As possess outstanding hydroxylating activity to fatty acids such as myristic acid. Other CYP102 subfamily members share substrate specificity of CYP102As, but, occasionally, unusual characteristics of its own subfamily have been found. In this study, only one self-sufficient cytochrome P450 from Streptomyces cattleya was renamed from CYP102A_scat to CYP102G4, purified and characterized. UV-Vis spectrometry pattern, FAD/FMN analysis, and protein sequence comparison among CYP102s have shown that CYP102 from Streptomyces cattleya belongs to CYP102G subfamily...
August 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28820887/identification-of-putative-qtls-for-seedling-stage-phosphorus-starvation-response-in-finger-millet-eleusine-coracana-l-gaertn-by-association-mapping-and-cross-species-synteny-analysis
#5
M Ramakrishnan, S Antony Ceasar, K K Vinod, V Duraipandiyan, T P Ajeesh Krishna, Hari D Upadhyaya, N A Al-Dhabi, S Ignacimuthu
A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P) responses by growing them in P sufficient (Psuf) and P deficient (Pdef) treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants...
2017: PloS One
https://www.readbyqxmd.com/read/28820269/reaction-phenotyping-to-assess-victim-drug-drug-interaction-risks
#6
Li Di
Reaction phenotyping provides critical information regarding the fraction metabolized (fm) of drug candidates. It has become increasingly important in drug discovery and development as it can be used to assess victim drug-drug interaction potential, guide structural modification to reduce fm, inform clinical study design, predict individual variability in pharmacokinetics, and evaluate the impact of genetic polymorphisms. Areas covered: The currently available in vitro and in vivo methods for reaction phenotyping are summarized along with their advantages, limitations and timings for application during the different stages of drug discovery and development...
August 18, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28819233/biology-physiology-and-gene-expression-of-grasshopper-oedaleus-asiaticus-exposed-to-diet-stress-from-plant-secondary-compounds
#7
Xunbing Huang, Jingchuan Ma, Xinghu Qin, Xiongbing Tu, Guangchun Cao, Guangjun Wang, Xiangqun Nong, Zehua Zhang
We studied the role of plant primary and secondary metabolites in mediating plant-insect interactions by conducting a no-choice single-plant species field experiment to compare the suitability, enzyme activities, and gene expression of Oedaleus asiaticus grasshoppers feeding on four host and non-host plants with different chemical traits. O. asiaticus growth showed a positive relationship to food nutrition content and a negative relationship to secondary compounds content. Grasshopper amylase, chymotrypsin, and lipase activities were positively related to food starch, crude protein, and lipid content, respectively...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819225/cytochrome-p450-abc-transporter-inhibition-simultaneously-enhances-ivermectin-pharmacokinetics-in-the-mammal-host-and-pharmacodynamics-in-anopheles-gambiae
#8
Carlos J Chaccour, Felix Hammann, Marta Alustiza, Sandra Castejon, Brian B Tarimo, Gloria Abizanda, Ángel Irigoyen Barrio, Helena Martí Soler, Rafael Moncada, José Ignacio Bilbao, Azucena Aldaz, Marta Maia, José Luis Del Pozo
Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818751/nutritional-modulation-of-intestinal-drug-metabolizing-cytochrome-p450-by-butyrate-of-different-origin-in-chicken
#9
Anna Kulcsár, Gábor Mátis, Andor Molnár, Janka Petrilla, László Wágner, Hedvig Fébel, Ferenc Husvéth, Károly Dublecz, Zsuzsanna Neogrády
Intestinal cytochrome P450 (CYP) enzymes play key role in the first pass metabolism of orally ingested xenobiotics, providing a primary metabolic barrier, being of special importance in maintaining animal health and production. This study was aimed to investigate how intestinal drug-metabolizing CYPs can be modulated by nutritional factors in broiler chicken. We investigated the effects of the natural growth promoter (n-)butyrate of different origin (feed supplementation of protected or non-protected forms and/or inducing caecal microbial production by supporting higher level of dietary non-starch polysaccharides [NSP]) on the activity of duodenal CYPs...
August 1, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28818427/molecular-cloning-and-functional-characterization-of-nadph-dependent-cytochrome-p450-reductase-from-the-green-microalga-botryococcus-braunii-b-race
#10
Chung-Yau Tsou, Shigeki Matsunaga, Shigeru Okada
The green microalga Botryococcus braunii of the B race accumulates various lipophilic compounds containing a 10,11-oxidosqualene epoxide moiety in addition to large amounts of triterpene hydrocarbons. While 2,3-squalene epoxidases have already been isolated and characterized from the alga, the enzyme that catalyzes the 10,11-epoxidation of squalene has remained elusive. In order to obtain a molecular tool to explore a 10,11-squalene epoxidase, cDNA cloning of an NADPH-dependent cytochrome P450 reductase (CPR) that is required by both squalene epoxidases and cytochrome P450 enzymes was carried out...
August 14, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28815728/effects-of-bifenthrin-exposure-on-the-estrogenic-and-dopaminergic-pathways-in-zebrafish-embryos-and-juveniles
#11
Luísa Becker Bertotto, Jaben Richards, Jay Gan, David Christopher Volz, Daniel Schlenk
Bifenthrin (BF) is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of BF increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic (DA) pathway components. DA neurons can indirectly regulate E2 biosynthesis, suggesting that BF may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Since embryos do not have a complete HPG axis, the hypothesis that BF impairs DA regulation was tested in embryonic and one-month old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0...
August 16, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28814868/nano-sized-cytochrome-p450-3a4-inhibitors-to-block-hepatic-metabolism-of-docetaxel
#12
Marion Paolini, Laurence Poul, Céline Berjaud, Matthieu Germain, Audrey Darmon, Maxime Bergère, Agnès Pottier, Laurent Levy, Eric Vibert
Most drugs are metabolized by hepatic cytochrome P450 3A4 (CYP3A4), resulting in their reduced bioavailability. In this study, we present the design and evaluation of bio-compatible nanocarriers trapping a natural CYP3A4-inhibiting compound. Our aim in using nanocarriers was to target the natural CYP3A4-inhibiting agent to hepatic CYP3A4 and leave drug-metabolizing enzymes in other organs undisturbed. In the design of such nanocarriers, we took advantage of the nonspecific accumulation of small nanoparticles in the liver...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28814372/association-of-cyp19a1-gene-polymorphisms-with-anoestrus-in-water-buffaloes
#13
Khairy M El-Bayomi, Ayman A Saleh, Ashraf Awad, Mahmoud S El-Tarabany, Hadeel S El-Qaliouby, Mohamed Afifi, Shymaa El-Komy, Walaa M Essawi, Essam A Almadaly, Mohammed A El-Magd
Cytochrome P450 aromatase (encoded by the CYP19A1 gene) regulates oestrogen biosynthesis and so plays an essential role in female fertility. We investigated the genetic association of CYP19A1 with the risk of anoestrus in Egyptian water buffaloes. A total of 651 animals (326 anoestrous and 325 cycling) were used in this case-control study. Using single-strand conformation polymorphisms and sequencing, four single nucleotide polymorphisms (SNPs) were detected; c.-135T>C SNP in the 5'UTR and three non-synonymous SNPs: c...
August 17, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28812950/expression-of-cytochrome-p450-regulators-in-cynomolgus-macaque
#14
Yasuhiro Uno, Hiroshi Yamazaki
1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed seventeen P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of seventeen P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered, with the human orthologs...
August 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28812125/recombinant-expression-and-biochemical-characterization-of-mycobacterium-tuberculosis-3fe-4s-ferredoxin-rv1786
#15
Yun Lu, Feng Qiao, Yue Li, Xiao-Hong Sang, Cong-Ran Li, Jian-Dong Jiang, Xin-Yi Yang, Xue-Fu You
Ferredoxins are iron-sulfur protein that mediate electron transfer in cytochrome P450 mono-oxygenase (CYP)-related catalytic reactions in a wide variety of organisms. Rv1786 is a putative ferredoxin, encoded by a gene located downstream of the gene encoding CYP143A1 in the Mycobacterium tuberculosis genome. However, the structure and function of Rv1786 have remained unclear. Here, the recombinant Mtb Rv1786 was expressed, purified as a His-tagged form and characterized with [3Fe-4S] clusters as its cofactors using a series of measurements including SDS-PAGE, western blot, UV/Visible, MALDI-TOF/TOF-MS, and electron paramagnetic resonance spectroscopic analysis...
August 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28811501/characterisation-of-sterol-biosynthesis-and-validation-of-14%C3%AE-demethylase-as-a-drug-target-in-acanthamoeba
#16
Scott Thomson, Christopher A Rice, Tong Zhang, RuAngelie Edrada-Ebel, Fiona L Henriquez, Craig W Roberts
The soil amoebae Acanthamoeba causes Acanthamoeba keratitis, a severe sight-threatening infection of the eye and the almost universally fatal granulomatous amoebic encephalitis. More effective treatments are required. Sterol biosynthesis has been effectively targeted in numerous fungi using azole compounds that inhibit the cytochrome P450 enzyme sterol 14α-demethylase. Herein, using Gas Chromatography Mass Spectrometry (GCMS), we demonstrate that the major sterol of Acanthamoeba castellanii is ergosterol and identify novel putative precursors and intermediate sterols in its production...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810587/association-of-polycystic-ovary-syndrome-with-metabolic-syndrome-and-gestational-diabetes-aggravated-complication-of-pregnancy
#17
Kui Yao, Ce Bian, Xia Zhao
Polycystic ovary syndrome (PCOS) affects 5-20% of the reproductive age women globally. PCOS is diagnosed by the presence of hyperandrogenism, oligo-anovulation, and polycystic morphology of at least one ovary. Insulin resistance (IR), hyperinsulinemia and associated metabolic abnormalities including metabolic syndrome play a significant role in the development of PCOS. The chances of developing MS in PCOS women was shown to increase by almost 14-fold in patients with increasing body mass index. Even in the absence of overt obesity, a preferential deposition of intra-abdominal fat is noted in PCOS women and this intra-abdominal fat leads to impaired insulin action and functional IR and hyperandrogenism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810573/warfarin-induced-life-threatening-bleeding-associated-with-a-cyp3a4-loss-of-function-mutation-in-an-acute-limb-ischemia-patient-case-report-and-review-of-the-literature
#18
Xiao-Wei Ma, Chang-Ning Hao, Zhi-Chun Gu, Meng Ye, Min Li, Lan Zhang
Patients with acute limb ischemia, deep venous thrombosis and pulmonary artery embolism may be treated with warfarin. The dose-response interaction of warfarin is associated with numerous factors, depending on which an uncommon life-threatening bleeding may occur. The present case study reported on a patient with acute limb ischemia and a history of warfarin-induced bleeding ten years previously and who again developed life threatening bleeding associated with warfarin treatment and received vascular surgery...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808417/down-regulation-of-aminopeptidase-n-and-abc-transporter-subfamily-g-transcripts-in-cry1ab-and-cry1ac-resistant-asian-corn-borer-ostrinia-furnacalis-lepidoptera-crambidae
#19
Tiantao Zhang, Brad S Coates, Yueqin Wang, Yidong Wang, Shuxiong Bai, Zhenying Wang, Kanglai He
The Asian corn borer (ACB), Ostrinia furnacalis (Lepidoptera: Crambidae), is a highly destructive pest of cultivated maize throughout East Asia. Bacillus thuringiensis (Bt) crystalline protein (Cry) toxins cause mortality by a mechanism involving pore formation or signal transduction following toxin binding to receptors along the midgut lumen of susceptible insects, but this mechanism and mutations therein that lead to resistance are not fully understood. In the current study, quantitative comparisons were made among midgut expressed transcripts from O...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808272/a-combinatorial-approach-for-the-discovery-of-cytochrome-p450-2d6-inhibitors-from-nature
#20
Johannes Hochleitner, Muhammad Akram, Martina Ueberall, Rohan A Davis, Birgit Waltenberger, Hermann Stuppner, Sonja Sturm, Florian Ueberall, Johanna M Gostner, Daniela Schuster
The human cytochrome P450 2D6 (CYP2D6) enzyme is part of phase-I metabolism and metabolizes at least 20% of all clinically relevant drugs. Therefore, it is an important target for drug-drug interaction (DDI) studies. High-throughput screening (HTS) assays are commonly used tools to examine DDI, but show certain drawbacks with regard to their applicability to natural products. We propose an in silico - in vitro workflow for the reliable identification of natural products with CYP2D6 inhibitory potential. In order to identify candidates from natural product-based databases that share similar structural features with established inhibitors, a pharmacophore model was applied...
August 14, 2017: Scientific Reports
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