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https://www.readbyqxmd.com/read/29454001/brain-bioenergetics-in-rats-with-acute-hyperphenylalaninemia
#1
Nádia Weber Dimer, Bruna Klippel Ferreira, Jotele Fontana Agostini, Maria Luiza Gomes, Luiza Wilges Kist, Fernanda Malgarin, Milena Carvalho-Silva, Lara Mezari Gomes, Joyce Rebelo, Marisa Jádna Silva Frederico, Fátima Regina Mena Barreto Silva, Eduardo Pacheco Rico, Mauricio Reis Bogo, Emilio Luiz Streck, Gustavo Costa Ferreira, Patrícia Fernanda Schuck
Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism caused by deficient phenylalanine hydroxylase activity. The deficiency results in increased levels of Phe and its metabolites in fluids and tissues of patients. PKU patients present neurological signals and symptoms including hypomyelination and intellectual deficit. This study assessed brain bioenergetics at 1 h after acute Phe administration to induce hyperphenylalaninemia (HPA) in rats. Wistar rats were randomized in two groups: HPA animals received a single subcutaneous administration of Phe (5...
February 14, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29453678/differential-expression-of-the-tweak-receptor-fn14-in-idh1-wild-type-and-mutant-gliomas
#2
David S Hersh, Sen Peng, Jimena G Dancy, Rebeca Galisteo, Jennifer M Eschbacher, Rudy J Castellani, Jonathan E Heath, Teklu Legesse, Anthony J Kim, Graeme F Woodworth, Nhan L Tran, Jeffrey A Winkles
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme...
February 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29453450/insights-into-the-inhibitory-mechanisms-of-nadh-on-the-%C3%AE-%C3%AE-heterodimer-of-human-nad-dependent-isocitrate-dehydrogenase
#3
Yabing Liu, Lejia Hu, Tengfei Ma, Jun Yang, Jianping Ding
Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the oxidative decarboxylation of isocitrate in the citric acid cycle. In the α 2 βγ heterotetramer of NAD-IDH, the γ subunit plays the regulatory role and the β subunit the structural role. Previous biochemical data have shown that mammalian NAD-IDHs can be inhibited by NADH; however, the molecular mechanism is unclear. In this work, we show that the αβ, αγ and α 2 βγ enzymes of human NAD-IDH can be inhibited by NADH, and further determine the crystal structure of the αγ heterodimer bound with an Mg 2+ and an NADH at the active site and an NADH at the allosteric site, which resembles that of the inactive α Mg γ heterodimer...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453319/leptin-signaling-mediates-obesity-associated-csc-enrichment-and-emt-in-preclinical-tnbc-models
#4
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453060/effect-of-selenium-on-penaeus-monodon-and-perna-viridis-enzyme-activities-and-histopathological-responses
#5
Avula Nagarjuna, Panneerselvam Karthikeyan, Dhandapani Mohan, Shambanagouda Rudragouda Marigoudar
The study was carried out to evaluate enzyme activities and histopathological changes due to the effect of acute and chronic definitive toxicity of selenium (Se) on the post larvae (PL) of giant tiger shrimp (Penaeus monodon), and green mussel (Perna viridis). The 96-h Median Lethal concentration (LC 50 ) for the PL of shrimp was 3.36 mg L -1 and the chronic value for the long-term survival endpoint in a 21-d exposure was 0.10 mg L -1 . The green mussel 96-h LC 50 was 28.41 mg L -1 and the chronic value for the long-term survival endpoint in a 30-d exposure was 3...
February 10, 2018: Chemosphere
https://www.readbyqxmd.com/read/29452639/mitochondrial-mdm2-regulates-respiratory-complex-i-activity-independently-of-p53
#6
Giuseppe Arena, Madi Yann Cissé, Samuel Pyrdziak, Laurent Chatre, Romain Riscal, Maryse Fuentes, Jamie Jon Arnold, Markus Kastner, Laurie Gayte, Christelle Bertrand-Gaday, Kevin Nay, Claire Angebault-Prouteau, Kerren Murray, Beatrice Chabi, Christelle Koechlin-Ramonatxo, Béatrice Orsetti, Charles Vincent, François Casas, Jean-Christophe Marine, Sandrine Etienne-Manneville, Florence Bernex, Anne Lombès, Craig Eugene Cameron, Hervé Dubouchaud, Miria Ricchetti, Laetitia Karine Linares, Laurent Le Cam
Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452638/nadh-shuttling-couples-cytosolic-reductive-carboxylation-of-glutamine-with-glycolysis-in-cells-with-mitochondrial-dysfunction
#7
Edoardo Gaude, Christina Schmidt, Payam A Gammage, Aurelien Dugourd, Thomas Blacker, Sew Peak Chew, Julio Saez-Rodriguez, John S O'Neill, Gyorgy Szabadkai, Michal Minczuk, Christian Frezza
The bioenergetics and molecular determinants of the metabolic response to mitochondrial dysfunction are incompletely understood, in part due to a lack of appropriate isogenic cellular models of primary mitochondrial defects. Here, we capitalize on a recently developed cell model with defined levels of m.8993T>G mutation heteroplasmy, mTUNE, to investigate the metabolic underpinnings of mitochondrial dysfunction. We found that impaired utilization of reduced nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain leads to cytosolic reductive carboxylation of glutamine as a new mechanism for cytosol-confined NADH recycling supported by malate dehydrogenase 1 (MDH1)...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452393/no-copper-supplementation-in-a-corn-soybean-basal-diet-has-no-adverse-effects-on-late-phase-laying-hens-under-normal-and-cyclic-high-temperatures
#8
W X Li, Y Q Chen, L H Zhao, Q G Ma, J Y Zhang, C Ji
Over supplementation of copper (Cu) in animal diets may cause serious pollution in soil, water and harvested crops. To minimize the potential pollution, the effects of corn-soybean basal diet with or without supplementation of 8 mg Cu/kg on laying performance, plasma biochemical metabolic indices, and antioxidant status in laying hens were evaluated under normal and cyclic high temperatures. A total of 240 Hy-Line Brown laying hens were randomly allotted to 4 treatments with 6 replicates of 10 hens per replicate according to factorial design involved in 2 temperatures [normal temperature (NT) vs...
February 14, 2018: Poultry Science
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#9
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29452288/repetitive-tlr-3-activation-in-the-lung-induces-skeletal-muscle-adaptations-and-cachexia
#10
Ted G Graber, Brandy L Rawls, Bing Tian, William J Durham, Camille R Brightwell, Allan R Brasier, Blake B Rasmussen, Christopher S Fry
Due to immunosenescence, older adults are particularly susceptible to lung-based viral infections, with increased severity of symptoms in those with underlying chronic lung disease. Repeated respiratory viral infections produce lung maladaptations, accelerating pulmonary dysfunction. Toll like 3 receptor (TLR3) is a membrane protein that senses exogenous double-stranded RNA to activate the innate immune response to a viral infection. Polyinosinic-polycytidylic acid [poly(I:C)] mimics double stranded RNA and has been shown to activate TLR3...
February 13, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29450727/metabolic-implications-of-hypoxia-and-pseudohypoxia-in-pheochromocytoma-and-paraganglioma
#11
REVIEW
Katarina Kluckova, Daniel A Tennant
Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant phenotypes such as epithelial-mesenchymal transition, stem cell-like characteristics and metabolic transformation. However, hypoxia-associated phenotypes are often observed in cancer in the absence of hypoxia, a phenotype known as pseudohypoxia, which is very well documented in specific tumour types, including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL tumours carry a germ line mutation in one of a number of susceptibility genes of which those that are found in succinate dehydrogenase (SDH) or in von Hippel-Lindau (VHL) genes manifest a strong pseudohypoxic phenotype...
February 15, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29450259/hand-assisted-laparoscopic-partial-nephrectomy-for-large-renal-carcinoma-with-succinate-dehydrogenase-deficiency
#12
Ann Buhl Bersang, Sarah Bube, Mikkel Fode, Nessn H Azawi
Background: Germline mutations in succinate dehydrogenase (SDH) are associated with multifocal cancers: pituitary gland tumors, pheochromocytomas, paragangliomas, gastrointestinal stromal tumors, and renal-cell carcinomas (RCCs). SDH-deficient renal-cell carcinoma (SDH-RCC) was first identified in 2004 as an inherited kidney cancer with mutations in the SDH gene. SDH consists of A, B, C, and D units. Mutation in the SDHB gene is the most common mutation in SDH-deficient RCCs. Case Presentation: We report a case of a 51-year-old healthy man diagnosed with SDHB germline mutation and RCCs...
2018: Journal of Endourology Case Reports
https://www.readbyqxmd.com/read/29450143/purified-horse-milk-exosomes-contain-an-unpredictable-small-number-of-major-proteins
#13
Sergey E Sedykh, Lada V Purvinish, Artem S Monogarov, Evgeniya E Burkova, Alina E Grigor'eva, Dmitrii V Bulgakov, Pavel S Dmitrenok, Valentin V Vlassov, Elena I Ryabchikova, Georgy A Nevinsky
Exosomes are 40-100 nm nanovesicles containing RNA and different proteins. Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in intracellular communication and immune function. Exosomes from different sources are usually obtained by combination of centrifugation and ultracentrifugation and according to published data can contain from a few dozens to thousands of different proteins. Crude exosome preparations from milk of eighteen horses were obtained for the first time using several standard centrifugations...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449614/decreased-succinate-dehydrogenase-b-in-human-hepatocellular-carcinoma-accelerates-tumor-malignancy-by-inducing-the-warburg-effect
#14
Po-Lin Tseng, Wei-Hsuan Wu, Tsung-Hui Hu, Chih-Wei Chen, Hung-Chi Cheng, Chien-Feng Li, Wen-Hui Tsai, Hui-Ju Tsai, Meng-Che Hsieh, Jiin-Haur Chuang, Wen-Tsan Chang
Changes in TCA cycle enzymes or respiratory activity are possible mechanisms of aerobic glycolysis that contributes to tumor progression. To clarify whether the decrease of succinate dehydrogenase B (SDHB) alters energy metabolism, induces the Warburg effect and results in tumor malignancy, SDHB expression was examined and modulated in hepatocellular carcinoma (HCC) tissues and cells, respectively. SDHB level was often decreased in malignant HCC cells and tissues. Furthermore, the reduced SDHB expression was associated with advanced tumor stage and poor survival rate...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449592/first-evidence-for-a-multienzyme-complex-of-lipid-biosynthesis-pathway-enzymes-in-cunninghamella-bainieri
#15
Shuwahida Shuib, Izyanti Ibrahim, Mukram Mohamed Mackeen, Colin Ratledge, Aidil Abdul Hamid
Malic enzyme (ME) plays a vital role in determining the extent of lipid accumulation in oleaginous fungi being the major provider of NADPH for the activity of fatty acid synthase (FAS). We report here the first direct evidence of the existence of a lipogenic multienzyme complex (the lipid metabolon) involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and lipid accumulation phases were prepared by protoplasting and subjected to Blue Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449156/stochastic-expression-of-lactate-dehydrogenase-a-induces-escherichia-coli-persister-formation
#16
Naoki Yamamoto, Rino Isshiki, Yuto Kawai, Daiki Tanaka, Tetsushi Sekiguchi, Shinya Matsumoto, Satoshi Tsuneda
Bacterial persisters are phenotypic variants that survive the treatment of lethal doses of growth-targeting antibiotics without mutations. Although the mechanism underlying persister formation has been studied for decades, how the persister phenotype is switched on and protects itself from antibiotics has been elusive. In this study, we focused on the lactate dehydrogenase gene (ldhA) that was upregulated in an Escherichia coli persister-enriched population. A survival rate assay using an ldhA-overexpressing strain showed that ldhA expression induced persister formation...
February 12, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29449005/association-between-oxidative-stress-genetic-factors-and-clinical-severity-in-children-with-sickle-cell-anemia
#17
Céline Renoux, Philippe Joly, Camille Faes, Pauline Mury, Buse Eglenen, Mine Turkay, Gokce Yavas, Ozlem Yalcin, Yves Bertrand, Nathalie Garnier, Daniela Cuzzubbo, Alexandra Gauthier, Marc Romana, Berenike Möckesch, Giovanna Cannas, Sophie Antoine-Jonville, Vincent Pialoux, Philippe Connes
OBJECTIVES: To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. STUDY DESIGN: Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sβ 0 )...
February 13, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29448201/trace-element-dynamics-of-biosolids-derived-microbeads
#18
Hasintha Wijesekara, Nanthi S Bolan, Lauren Bradney, Nadeeka Obadamudalige, Balaji Seshadri, Anitha Kunhikrishnan, Rajarathnam Dharmarajan, Yong Sik Ok, Jörg Rinklebe, M B Kirkham, Meththika Vithanage
This study focused on quantifying and characterising microbeads in biosolids (i.e., treated sewage sludge), and in examining interactions of microbeads with trace elements when biosolids are added to soil. Under laboratory conditions, batch experiments were conducted to investigate the adsorption of Cu onto pure and surface modified microbeads suspended in soil. The ecotoxicity of microbead-metal complexes to soil microbial activities was also investigated by monitoring basal respiration and dehydrogenase activity...
February 1, 2018: Chemosphere
https://www.readbyqxmd.com/read/29448107/decrease-in-the-cytosolic-nadp-dependent-isocitrate-dehydrogenase-activity-through-porcine-sperm-capacitation
#19
Yuki Katoh, Michiko Tamba, Manabu Matsuda, Kazuhiro Kikuchi, Naomichi Okamura
In order to understand the molecular mechanisms involved in the sperm capacitation, we have identified the proteins tyrosine-phosphorylated during the capacitation especially in conjunction with the regulation of the levels of reactive oxygen species (ROS) in sperm. In the present study, the effects of the tyrosine phosphorylation of cytosolic NADP + -dependent isocitrate dehydrogenase (IDPc) on its catalytic activity and on the levels of ROS in sperm have been studied. The tyrosine phosphorylated IDPc showed a significantly lowered enzymatic activity...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29448103/fgf-21-deficiency-slows-gastric-emptying-and-reduces-initial-blood-alcohol-concentration-in-mice-exposed-to-acute-alcohol-in-fasting-state
#20
Guicheng Wu, Yanlong Liu, Yunhuan Liu, Lihua Zhang, Haiyang Zhao, Liming Liu, Cuiqing Zhao, Wenke Feng
Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild time (WT) control mice were divided into two groups and fasted for 24 h followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage...
February 12, 2018: Biochemical and Biophysical Research Communications
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