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https://www.readbyqxmd.com/read/29336038/a-single-nucleotide-polymorphism-in-the-canine-cytochrome-b5-reductase-cyb5r3-gene-is-associated-with-sulfonamide-hypersensitivity-and-is-overrepresented-in-doberman-pinschers
#1
J M Reinhart, J Ekena, A C Cioffi, L A Trepanier
Canine sulfonamide hypersensitivity (HS) has been associated with a variant in the cytochrome b5 reductase gene (CYB5R3 729A>G), which encodes a drug-detoxifying enzyme. Study objectives were to determine variant allele frequency in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS, and to characterize the effects of CYB5R3 729G on gene expression and function. CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs. non-Doberman (non-DOBE; n = 60) dogs...
January 15, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29328974/novel-approach-for-evaluating-pharmaceuticals-toxicity-using-daphnia-model-analysis-of-the-mode-of-cytochrome-p450-generated-metabolite-action-after-acetaminophen-exposure
#2
Ryeo-Ok Kim, Min-A Jo, Jinhaeng Song, Il-Chan Kim, Seokjoo Yoon, Woo-Keun Kim
Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity...
December 30, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29327817/ketonization-of-proline-residues-in-the-peptide-chains-of-actinomycins-by-a-4-oxoproline-synthase
#3
Siamak Semsary, Ivana Crnovčić, Ronja Driller, Joachim Vater, Bernhard Loll, Ullrich Keller
X-type actinomycins (Acms) contain 4-hydroxyproline (Acm X0) or 4-oxoproline (Acm X2) in their ß-pentapeptide lactone rings whereas their α-ring contains proline. We demonstrate that these Acms are formed through asymmetric condensation of Acm half molecules (Acm halves) containing proline with 4-hydroxyproline- or 4-oxo-proline-containing Acm halves. In turn we show - using an artificial Acm half analogue (PPL 1) with proline in its peptide chain - its conversion into the 4-hydroxyproline and 4-oxoproline-containing Acm halves, PPL 0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus...
January 12, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29326229/genomic-understanding-of-an-infectious-brain-disease-from-the-desert
#4
Leandro F Moreno, Abdalla A O Ahmed, Balázs Brankovics, Christina A Cuomo, Steph B J Menken, Saad J Taj-Aldeen, Hani Faidah, J Benjamin Stielow, Marcus de M Teixeira, Francesc X Prenafeta-Boldú, Vania A Vicente, Sybren de Hoog
Rhinocladiella mackenziei accounts for the majority of fungal brain infections in the Middle East and is restricted to the arid climate zone between Saudi Arabia and Pakistan. Neurotropic dissemination caused by this fungus has been reported in immunocompromised, but also immunocompetent individuals. If untreated, the infection is fatal. Outside of humans, the environmental niche of R. mackenziei is unknown, and the fungus has been only cultured from brain biopsies. In this paper we describe the whole genome re-sequencing of two Rhinocladiella mackenziei strains from patients in Saudi Arabia and Qatar...
January 11, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29317847/pharmacogenetic-guidance-individualized-medicine-promotes-enhanced-pain-outcomes
#5
Lisa Lynn Dragic, Erica L Wegrzyn, Michael E Schatman, Jeffrey Fudin
The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#6
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296229/selenium-against-lead-induced-apoptosis-in-chicken-nervous-tissues-via-mitochondrial-pathway
#7
Yihao Zhu, Xiaoyan Jiao, Yang An, Shu Li, Xiaohua Teng
To investigate alleviative effect of selenium (Se) on lead (Pb)-induced apoptosis in chicken nervous tissues, 7-day-old chickens were randomly divided into four groups. The control group was fed a standard diet and drinking water. In the Pb and Se/Pb groups, (CH3OO)2Pb was dissolved in drinking water. In the Se and Se/Pb groups, Na2SeO3 was put into the standard diet. Embryonic neurocytes were divided into the control, Se (containing Na2SeO3), Pb (containing (CH3COO)2Pb), and Se/Pb (containing Na2SeO3 and (CH3COO)2Pb) groups...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288567/isothiocyanates-and-xenobiotic-detoxification
#8
REVIEW
Ahmad Faizal Abdull Razis, Nattaya Konsue, Costas Ioannides
The potential of isothiocyanates to antagonise the carcinogenicity of structurally-diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators...
December 30, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29286073/proteasome-inhibition-protects-against-diet-induced-gallstone-formation-through-modulation-of-cholesterol-and-bile-acid-homeostasis
#9
Eun-Ji Lee, Min Hee Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Gallstone disease is one of the most prevalent and costly gastrointestinal disorders worldwide. Gallstones are formed in the biliary system by cholesterol secretions in bile, which result from excess cholesterol, a deficiency in bile salts or a combination of the two. The present study examined the effects of proteasome inhibition on gallstone formation using the proteasome inhibitors bortezomib (BT) and carfilzomib (CF). C57BL/6J mice were fed a lithogenic diet to generate gallstones and injected with BT or CF for 12 weeks...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285101/proteomic-changes-of-cd4-cd25-forkhead-box-p3-regulatory-t-cells-in-a-30-day-rat-model-of-sepsis-survival
#10
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282292/the-radical-sam-protein-hemw-is-a-heme-chaperone
#11
Vera Haskamp, Simone Karrie, Toni Mingers, Stefan Barthels, François Alberge, Axel Magalon, Katrin Müller, Eckard Bill, Wolfgang Lubitz, Kirstin Kleeberg, Peter Schweyen, Martin Bröring, Martina Jahn, Dieter Jahn
Radical S-adenosylmethionine (SAM) enzymes exist in organisms from all kingdoms of life, and all of these proteins generate an adenosyl radical via the homolytic cleavage of the S-C(5') bond of SAM. Of particular interest are radical SAM enzymes, such as heme chaperones, that insert heme into respiratory enzymes. For example, heme chaperones insert heme into target proteins, but have been studied only for the formation of cytochrome c type hemoproteins. Here, we report that a radical SAM protein, the heme chaperone HemW from bacteria, is required for the insertion of heme b into respiratory chain enzymes...
December 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29277994/the-choreography-of-the-reductase-and-p450bm3-domains-towards-electron-transfer-is-instigated-by-the-substrate
#12
Kshatresh Dutta Dubey, Sason Shaik
The driving force for the electron transfer (ET) step in the catalytic cycle of cytochrome P450BM3, is investigated using three sets of 1 µs molecular dynamic simulations for the resting state of P450 in complex with the flavin (FMN) in the reductase domain. These sets involve: (i) substrate-free (SF), (ii) substrate (N-palmitoyl glycine, i.e NPG)-bound (SB), and (iii) SB with the semiquinone radical-anion (SQ-) of FMN. Starting from the X-ray structure of the SF heme domain, we observe that the α1 helix (of the reductase) and the C helix (of the heme) undergo reorientation to a parallel orientation, which is the thermochemically stable form...
December 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29277707/the-in-vitro-metabolism-of-11%C3%AE-hydroxyprogesterone-and-11-ketoprogesterone-to-11-ketodihydrotestosterone-in-the-backdoor-pathway
#13
Desmaré van Rooyen, Rachelle Gent, Lise Barnard, Amanda C Swart
Increased circulating 11β-hydroxyprogesterone (11OHP4), biosynthesised in the human adrenal, is associated with 21-hydroxylase deficiency in congenital adrenal hyperplasia. 17α-hydroxyprogesterone levels are also increased, with the steroid's metabolism to dihydrotestosterone in the backdoor pathway contributing to hyperandrogenic clinical conditions. In this study we investigated the in vitro biosynthesis and downstream metabolism of 11OHP4. Both cytochrome P450 11β-hydroxylase and aldosterone synthase catalyse the biosynthesis of 11OHP4 from progesterone (P4) which is converted to 11-ketoprogesterone (11KP4) by 11β-hydroxysteroid dehydrogenase type 2, while type 1 readily catalysed the reverse reaction...
December 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29276819/stabilization-of-the-reductase-domain-in-the-catalytically-self-sufficient-cytochrome-p450bm3-via-consensus-guided-mutagenesis
#14
Gloria Saab-Rincon, Hanan Alwaseem, Valeria Guzmán-Luna, Leticia Olvera, Rudi Fasan
The multi-domain, catalytically self-sufficient cytochrome P450 BM-3 from Bacillus megaterium (P450BM3) constitutes a versatile enzyme for the oxyfunctionalization of organic molecules and natural products. However, the limited stability of the diflavin reductase domain limits the utility of this enzyme for synthetic applications. In this work, a consensus-guided mutagenesis approach was applied to enhance the thermal stability of the reductase domain of P450BM3. Upon phylogenetic analysis of a set of distantly related P450s (% identity > 38%), a total of 14 amino acid substitutions were identified and evaluated in terms of their stabilizing effect relative to the wild-type reductase domain...
December 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29274033/supplementation-with-an-insoluble-fiber-obtained-from-carob-pod-ceratonia-siliqua-l-rich-in-polyphenols-prevents-dyslipidemia-in-rabbits-through-sirt1-pgc-1%C3%AE-pathway
#15
María Valero-Muñoz, Sandra Ballesteros, Baltasar Ruiz-Roso, Lourdes Pérez-Olleros, Beatriz Martín-Fernández, Vicente Lahera, Natalia de Las Heras
PURPOSE: To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver. METHODS: Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group)...
December 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29259615/silencing-of-d-lactate-dehydrogenase-impedes-glyoxalase-system-and-leads-to-methylglyoxal-accumulation-and-growth-inhibition-in-rice
#16
Baoguang An, Jie Lan, Xiaolong Deng, Silan Chen, Chao Ouyang, Huiyun Shi, Jing Yang, Yangsheng Li
D-Lactate is oxidized by two classes of D-lactate dehydrogenase (D-LDH), namely, NAD-dependent and NAD-independent D-LDHs. Little is known about the characteristics and biological functions of D-LDHs in rice. In this study, a functional NAD-independent D-LDH (LOC_Os07g06890) was identified in rice, as a result of alternative splicing events. Characterization of the expression profile, subcellular localization, and enzymatic properties of the functional OsD-LDH revealed that it is a mitochondrial cytochrome-c-dependent D-LDH with high affinity and catalytic efficiency...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29258871/phylogenetic-and-functional-characterization-of-ten-p450-genes-from-the-cyp6ae-subfamily-of-helicoverpa-armigera-involved-in-xenobiotic-metabolism
#17
Yu Shi, Huidong Wang, Zhi Liu, Shuwen Wu, Yihua Yang, René Feyereisen, Yidong Wu
The cotton bollworm, Helicoverpa armigera, is a generalist herbivore widely distributed over the world and is a major lepidopteran pest on cotton. Studies, especially from Asia, show that it relies on cytochrome P450 monooxygenases with broad substrate specificities to protect itself from pesticides. The number of P450s may have expanded in the processes of coping with the wide diversity of phytochemicals that the insect encounters among its numerous host plants. In order to examine the metabolic capabilities of these P450s, we focused here on all ten P450s of the Helicoverpa armigera CYP6AE subfamily, which can be easily induced by plant toxins and pyrethroids...
December 16, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29258585/effects-of-endurance-training-on-skeletal-muscle-mitochondrial-function-in-huntington-disease-patients
#18
Sandro Manuel Mueller, Saskia Maria Gehrig, Jens A Petersen, Sebastian Frese, Violeta Mihaylova, Maria Ligon-Auer, Natalia Khmara, Jean-Marc Nuoffer, André Schaller, Carsten Lundby, Marco Toigo, Hans H Jung
BACKGROUND: Mitochondrial dysfunction may represent a pathogenic factor in Huntington disease (HD). Physical exercise leads to enhanced mitochondrial function in healthy participants. However, data on effects of physical exercise on HD skeletal muscle remains scarce. We aimed at investigating adaptations of the skeletal muscle mitochondria to endurance training in HD patients. METHODS: Thirteen HD patients and 11 healthy controls completed 26 weeks of endurance training...
December 19, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29243009/adrenaline-induces-mitochondrial-biogenesis-in-rat-liver
#19
Gaetana Napolitano, Daniela Barone, Sergio Di Meo, Paola Venditti
We studied the effects of adrenaline administration and depletion (induced by reserpine) on rat liver oxidative metabolism. We showed that adrenaline increases, and reserpine decreases aerobic capacity (inferred by cytochrome oxidase activity) in tissue modifying the hepatic content of mitochondrial proteins without changing mitochondrial aerobic capacity. The changes in tissue cytochrome oxidase activity, which agreed with the expression levels of factors involved in mitochondrial biogenesis, such as PGC-1, NRF-1, and NRF-2, were associated with similar changes in tissue and mitochondrial State 3 respiration...
December 14, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29237573/identification-of-cytochrome-b5-cytb-5-1-and-cytb-5-2-in-c-elegans-evidence-for-differential-regulation-of-scd
#20
Baoshen He, Jingjing Zhang, Yanli Wang, Yamei Li, Xiaoju Zou, Bin Liang
Unsaturated fatty acids (UFAs) play crucial roles in living organisms regarding development, energy metabolism, stress resistance, etc. The biosynthesis of UFAs starts from the introduction of the first double bond by stearoyl-CoA desaturase (SCD), converting saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs). This desaturation is considered to be an aerobic process that requires cytochrome b5 reductase, cytochrome b5 and SCD. However, this enzyme system remains elusive in Caenorhabditis elegans...
December 10, 2017: Biochimica et Biophysica Acta
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