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Metabolic pathway

Amita Shukla-Dave, Mireia Castillo-Martin, Ming Chen, Jose Lobo, Nataliya Gladoun, Ana C Lorduy, Faisal M Khan, Vladimir Ponomarev, Zhengzi Yi, Weijia Zhang, Pier P Pandolfi, Hedvig Hricak, Carlos Cordon-Cardo
Increased polyamine synthesis is known to play an important role in prostate cancer. We aimed to explore its functional significance in prostate tumor initiation and its link to androgen receptor (AR) signaling. For this purpose, we generated a new cell line derived from normal epithelial prostate cells (RWPE-1) with overexpression of ornithine decarboxylase (ODC) and used it for in vitro and in vivo experiments. We then comprehensively analyzed the expression of the main metabolic enzymes of the polyamine pathway and spermine abundance in 120 well-characterized cases of human prostate cancer and high-grade prostate intraepithelial neoplasia (HGPIN)...
October 19, 2016: American Journal of Pathology
Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Zhuqing Leslie Li, Yonghui Shi, Yinyi Ding, Yumei Ran, Guowei Le
Oxidized tyrosine (O-Tyr) products have been detected in commercial food and have been demonstrated to induce liver injury in our previous study, but the precise mechanisms of the impact induced by dietary O-Tyr are still unclear. Kidney plays an important role in the metabolism of protein. Accumulation of O-Tyr products, especially the dityrosine (Dityr) and advanced oxidation protein products (AOPPs), in vivo was shown to be associated with many kidney diseases. Therefore, this study determined whether chronic exposure to dietary O-Tyr impaired renal function in rats...
October 21, 2016: Amino Acids
Raj Kumar Sharma, Kumudesh Mishra, Alvina Farooqui, Anu Behari, Vinay Kumar Kapoor, Neeraj Sinha
OBJECTIVE AND DESIGN: We present in this article (1)H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). MATERIAL/METHODS: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). (1)H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation...
October 21, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Ellen K Silbergeld
The microbiome is increasingly recognized as a critical component in human development, health, and disease. Its relevance to toxicology and pharmacology involves challenges to current concepts related to absorption, metabolism, gene:environment, and pathways of response. Framing testable hypotheses for experimental and epidemiological studies will require attention to study designs, biosampling, data analysis, and attention to confounders.
October 21, 2016: Toxicologic Pathology
Ruinan Gu, Fali Zhang, Gang Chen, Chaojun Han, Jay Liu, Zhaoxiang Ren, Yi Zhu, John L Waddington, Long Tai Zheng, Xuechu Zhen
Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis...
October 18, 2016: Brain, Behavior, and Immunity
Michaela L Sundqvist, Jon O Lundberg, Eddie Weitzberg
The nitrate-nitrite-nitric oxide pathway has emerged as a significant source of nitric oxide (NO) bioactivity. Dietary intake of inorganic nitrate has a number of cardiovascular effects as well as a decrease in oxygen cost during exercise and a reduction in resting metabolic rate (RMR). Oral bacteria have a key role in bioactivation of inorganic nitrate since they catalyse the conversion of salivary nitrate to the more reactive nitrite anion. Recent studies demonstrate that blood pressure increases with the use of an antiseptic mouthwash, indicating that endogenous, NO-synthase derived nitrate is recycled into nitrite and NO, sufficiently to modulate cardiovascular function...
October 18, 2016: Nitric Oxide: Biology and Chemistry
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
Alfred Amambua-Ngwa, Bakary Danso, Archibald Worwui, Sukai Ceesay, Nwakanma Davies, David Jeffries, Umberto D'Alessandro, David Conway
BACKGROUND: Previous genome-wide analyses of single nucleotide variation in Plasmodium falciparum identified evidence of an extended haplotype region on chromosome 6 in West Africa, suggesting recent positive selection. Such a pattern is not seen in samples from East Africa or South East Asia, so it could be marking a selective process specific to West Africa. Analyses of the haplotype structure in samples taken at different times could give clues to possible causes of selection. METHODS: This study investigates chromosome 6 extended haplotypes in The Gambia by analysing alleles at multiple microsatellite loci using genome sequence data previously obtained from clinical isolates collected in 2008, followed by genotyping of 13 loci in 439 isolates from 1984, 1991, 2008 and 2014...
October 21, 2016: Malaria Journal
Cheng-Fu Chang, Yi-Chao Lee, Kuen-Haur Lee, Hui-Ching Lin, Chia-Ling Chen, Che-Kun James Shen, Chi-Chen Huang
BACKGROUND: In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS...
October 21, 2016: Journal of Biomedical Science
Shengnan Zhai, Genying Li, Youwei Sun, Jianmin Song, Jihu Li, Guoqi Song, Yulian Li, Hongqing Ling, Zhonghu He, Xianchun Xia
BACKGROUND: Phytoene synthase 1 (PSY1) is the most important regulatory enzyme in carotenoid biosynthesis, whereas its function is hardly known in common wheat. The aims of the present study were to investigate Psy1 function and genetic regulation using reverse genetics approaches. RESULTS: Transcript levels of Psy1 in RNAi transgenic lines were decreased by 54-76 % and yellow pigment content (YPC) was reduced by 26-35 % compared with controls, confirming the impact of Psy1 on carotenoid accumulation...
October 21, 2016: BMC Plant Biology
Chaoyun Hao, Zhiqiang Xia, Rui Fan, Lehe Tan, Lisong Hu, Baoduo Wu, Huasong Wu
BACKGROUND: Piper nigrum L., or "black pepper", is an economically important spice crop in tropical regions. Black pepper production is markedly affected by foot rot disease caused by Phytophthora capsici, and genetic improvement of black pepper is essential for combating foot rot diseases. However, little is known about the mechanism of anti- P. capsici in black pepper. The molecular mechanisms underlying foot rot susceptibility were studied by comparing transcriptome analysis between resistant (Piper flaviflorum) and susceptible (Piper nigrum cv...
October 21, 2016: BMC Genomics
Pierre Dehoux, Jean Christophe Marvaud, Amr Abouelleil, Ashlee M Earl, Thierry Lambert, Catherine Dauga
BACKGROUND: Clostridium bolteae and Clostridium clostridioforme, previously included in the complex C. clostridioforme in the group Clostridium XIVa, remain difficult to distinguish by phenotypic methods. These bacteria, prevailing in the human intestinal microbiota, are opportunistic pathogens with various drug susceptibility patterns. In order to better characterize the two species and to obtain information on their antibiotic resistance genes, we analyzed the genomes of six strains of C...
October 21, 2016: BMC Genomics
Carly B Garrison, Kristin J Lastwika, Yuzheng Zhang, Christopher I Li, Paul D Lampe
Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding of signaling response during stress and disease. Large datasets, such as those obtained in high-dimensional proteomic studies, can be leveraged for pathway analysis to discover or describe the biological implications of clinical disease states. Obesity is a worldwide epidemic that is considered a risk factor for numerous other diseases. We performed analysis on plasma proteomic data from 3 separate sample sets of post-menopausal women to identify the pathways that are altered in subjects with a high body mass index (BMI) compared to normal BMI...
October 21, 2016: Journal of Proteome Research
Stacy-Anne Morgan, Dana C Nadler, Rayka Yokoo, David F Savage
Metabolic engineering offers the potential to renewably produce important classes of chemicals, particularly biofuels, at an industrial scale. DNA synthesis and editing techniques can generate large pathway libraries, yet identifying the best variants is slow and cumbersome. Traditionally, analytical methods like chromatography and mass spectrometry have been used to evaluate pathway variants, but such techniques cannot be performed with high throughput. Biosensors - genetically encoded components that actuate a cellular output in response to a change in metabolite concentration - are therefore a promising tool for rapid and high-throughput evaluation of candidate pathway variants...
October 18, 2016: Current Opinion in Chemical Biology
Aindrila Chatterjee, Janine Seyfferth, Jacopo Lucci, Ralf Gilsbach, Sebastian Preissl, Lena Böttinger, Christoph U Mårtensson, Amol Panhale, Thomas Stehle, Oliver Kretz, Abdullah H Sahyoun, Sergiy Avilov, Stefan Eimer, Lutz Hein, Nikolaus Pfanner, Thomas Becker, Asifa Akhtar
A functional crosstalk between epigenetic regulators and metabolic control could provide a mechanism to adapt cellular responses to environmental cues. We report that the well-known nuclear MYST family acetyl transferase MOF and a subset of its non-specific lethal complex partners reside in mitochondria. MOF regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA in aerobically respiring cells. MOF binds mtDNA, and this binding is dependent on KANSL3. The mitochondrial pool of MOF, but not a catalytically deficient mutant, rescues respiratory and mtDNA transcriptional defects triggered by the absence of MOF...
October 20, 2016: Cell
Timothy J Williams, Michelle Allen, Bernhard Tschitschko, Ricardo Cavicchioli
Haloarchaea are heterotrophic members of the Archaea that thrive in hypersaline environments, often feeding off the glycerol that is produced as an osmolyte by eucaryotic Dunaliella during primary production. In this study we analyzed glycerol metabolism genes in closed genomes of haloarchaea, and examined published data describing the growth properties of haloarchaea and experimental data for the enzymes involved. By integrating the genomic data with knowledge from the literature, we derived an understanding of the ecophysiology and evolutionary properties of glycerol catabolic pathways in haloarchaea...
October 21, 2016: Environmental Microbiology
Akira Shiraishi, Jun Murata, Erika Matsumoto, Shin Matsubara, Eiichiro Ono, Honoo Satake
Forsythia spp. are perennial woody plants which are one of the most extensively used medicinal sources of Chinese medicines and functional diets owing to their lignan contents. Lignans have received widespread attention as leading compounds in the development of antitumor drugs and healthy diets for reducing the risks of lifestyle-related diseases. However, the molecular basis of Forsythia has yet to be established. In this study, we have verified de novo deep transcriptome of Forsythia koreana leaf and callus using the Illumina HiSeq 1500 platform...
2016: PloS One
Durga Mahor, Anu Priyanka, Gandham S Prasad, Krishan Gopal Thakur
Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway...
2016: PloS One
Liane Balvedi Poersch-Bortolon, Jorge Fernando Pereira, Antonio Nhani, Hebert Hernán Soto Gonzáles, Gisele Abigail Montan Torres, Luciano Consoli, Rafael Augusto Arenhart, Maria Helena Bodanese-Zanettini, Márcia Margis-Pinheiro
Drought limits wheat production in the Brazilian Cerrado biome. In order to search for candidate genes associated to the response to water deficit, we analyzed the gene expression profiles, under severe drought stress, in roots and leaves of the cultivar MGS1 Aliança, a well-adapted cultivar to the Cerrado. A set of 4,422 candidate genes was found in roots and leaves. The number of down-regulated transcripts in roots was higher than the up-regulated transcripts, while the opposite occurred in leaves. The number of common transcripts between the two tissues was 1,249, while 2,124 were specific to roots and 1,049 specific to leaves...
October 20, 2016: Genetics and Molecular Biology
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