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https://www.readbyqxmd.com/read/29792813/metabolomics-reveals-the-molecular-mechanisms-of-copper-induced-cucumber-leaf-cucumis-sativus-senescence
#1
Lijuan Zhao, Yuxiong Huang, Kelly Paglia, Arpana Vaniya, Benjamin Wancewicz, Arturo A Keller
Excess copper may disturb plant photosynthesis and induce leaf senescence. The underlying toxicity mechanism is not well understood. Here, 3-week-old cucumber plants were foliar exposed to different copper concentrations (10, 100 and 500 mg/L) for a final dose of 0.21, 2.1 and 10 mg/plant, using CuSO4 as the Cu ion source for seven days, three times per day. Metabolomics quantified 149 primary and 79 secondary metabolites. A number of intermediates of the tricarboxylic acid (TCA) cycle were significantly down-regulated 1...
May 24, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29792435/measuring-drug-induced-changes-in-metabolite-populations-of-live-bacteria-real-time-analysis-by-raman-spectroscopy
#2
Paul R Carey, Grant R Whitmer, Michael J Yoon, Michael N Lombardo, Marianne Pusztai-Carey, Hossein Heidari-Torkabadi, Tao Che
Raman difference spectroscopy is shown to provide a wealth of molecular detail on changes within bacterial cells caused by infusion of antibiotics or hydrogen peroxide. E. coli strains paired with chloramphenicol, DHFR propargyl-based inhibitors, meropenem, or hydrogen peroxide provide details of the depletion of protein and nucleic acid populations in real time. Additionally, other reproducible Raman features appear and are attributed to changes in cell metabolite populations. An initial candidate for one of the metabolites involves population increases of citrate, an intermediate within the TCA cycle...
May 24, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29777685/thiamine-preserves-mitochondrial-function-in-a-rat-model-of-traumatic-brain-injury-preventing-inactivation-of-the-2-oxoglutarate-dehydrogenase-complex
#3
Garik V Mkrtchyan, Muammer Üçal, Andrea Müllebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I Bunik, Andrey V Kozlov
BACKGROUND AND PURPOSE: Based on the fact that traumatic brain injury is associated with mitochondrial dysfunction we aimed at localization of mitochondrial defect and attempted to correct it by thiamine. EXPERIMENTAL APPROACH: Interventional controlled experimental animal study was used. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion traumatic brain injury. Thiamine was administered 1 h prior to trauma; cortex was extracted for analysis 4 h and 3 d after trauma...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29775926/chlorophyll-a-%C3%AF-uorescence-and-transcriptome-reveal-the-toxicological-effects-of-bisphenol-a-on-an-invasive-cyanobacterium-cylindrospermopsis-raciborskii
#4
Rong Xiang, Junqiong Shi, Hongbo Zhang, Congcong Dong, Li Liu, JunKe Fu, Xinyu He, Yanjun Yan, Zhongxing Wu
Bisphenol A has attracted worldwide attention due to its harmful effects on humans, animals and plants. In this study, the toxicological effects of BPA on Cylindrospermopsis raciborskii were assessed based on chlorophyll a fluorescence and transcriptome analyses. The results showed that the growth of C. raciborskii was significantly inhibited when BPA exceeded 0.1 mg L-1 . A marked rise of phase J was observed at a concentration greater than 0.1 mg L-1 , while a K phase appeared at 20 mg L-1 . The chlorophyll a fluorescence parameters of RC/CS0 , F0 , φP0 , φE0 , and ψ0 , underwent a significant decline under all treatments of BPA, whereas a significant increase in both VJ and M0 occurred under all concentrations of BPA...
May 9, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29772792/metabolic-regulation-of-hypoxia-inducible-transcription-factors-the-role-of-small-molecule-metabolites-and-iron
#5
REVIEW
Peter S J Bailey, James A Nathan
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on the metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how tricarboxylic acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) and intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs)...
May 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772443/mir-92a-regulates-oral-squamous-cell-carcinoma-oscc-cell-growth-by-targeting-foxp1-expression
#6
Jun Guo, Ning Wen, Sefei Yang, Xiaohang Guan, Song Cang
Increasing evidence indicates that microRNAs dysregulation contributes to the development and progression of various human cancers, including oral squamous cell carcinoma (OSCC). However, little is known about the potential role of microRNA-92a (miR-92a) in OSCC. Thus, the aim of this study was to investigate the effects of miR-92a expression on OSCC cell growth, apoptosis and tumorigenesis. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-92a in primary tumor tissues and OSCC cell lines...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772230/replacing-c189-in-the-bzip-domain-of-zta-with-s-t-v-or-a-changes-dna-binding-specificity-to-four-types-of-double-stranded-dna
#7
Sreejana Ray, Desiree Tillo, Nima Assad, Aniekanabasi Ufot, Christopher Deppmann, Stewart R Durell, Aleksey Porollo, Charles Vinson
Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29769417/lactate-in-cardiogenic-shock-current-understanding-and-clinical-implications
#8
G M Kubiak, A R Tomasik, K Bartus, R Olszanecki, P Ceranowicz
Adenosine triphosphate (ATP) is an essential substrate metabolite in human beings. Mitochondrial oxidative phosphorylation provides > 95% of ATP with the remainder derived from glycolysis or tricarboxylic acid cycle (TCA). In normal hearts, acetyl-CoA is synthesized from the β-oxidation of free fatty acids (FFA) and the oxidation of pyruvate. Pyruvate is synthesized from glycolysis and can be submitted either for decarboxylation to acetyl-CoA or for dehydrogenation to lactate. Moreover, pyruvate, as well as lactate, plays a key role in aerobic glucose metabolism which is highly dependent on ubiquitous regulatory mechanisms...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29768191/loss-of-a-negative-regulator-of-mtorc1-induces-aerobic-glycolysis-and-altered-fiber-composition-in-skeletal-muscle
#9
Paul A Dutchak, Sandi J Estill-Terpack, Abigail A Plec, Xiaozheng Zhao, Chendong Yang, Jun Chen, Bookyung Ko, Ralph J Deberardinis, Yonghao Yu, Benjamin P Tu
The conserved GATOR1 complex consisting of NPRL2-NPRL3-DEPDC5 inhibits mammalian target of rapamycin complex 1 (mTORC1) in response to amino acid insufficiency. Here, we show that loss of NPRL2 and GATOR1 function in skeletal muscle causes constitutive activation of mTORC1 signaling in the fed and fasted states. Muscle fibers of NPRL2 knockout animals are significantly larger and show altered fiber-type composition, with more fast-twitch glycolytic and fewer slow-twitch oxidative fibers. NPRL2 muscle knockout mice also have altered running behavior and enhanced glucose tolerance...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767961/real-time-monitoring-of-tricarboxylic-acid-metabolites-in-exhaled-breath
#10
Alberto Tejero Rioseras, Kapil Dev Singh, Nora Nowak, Martin T Gaugg, Tobias Bruderer, Renato Zenobi, Pablo M-L Sinues
The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids. Alteration in intracellular levels of its intermediates has been linked with a wide range of illnesses ranging from cancer to cellular necrosis or liver cirrhosis. Therefore, there exists an intrinsic interest in monitoring such metabolites...
May 16, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29766441/metabolomic-analysis-and-biochemical-changes-in-the-urine-and-serum-of-streptozotocin-induced-normal-and-obese-diabetic-rats
#11
Ahmed Mediani, Faridah Abas, M Maulidiani, Azliana Abu Bakar Sajak, Alfi Khatib, Chin Ping Tan, Intan Safinar Ismail, Khozirah Shaari, Amin Ismail, N H Lajis
Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1 H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated...
May 15, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29761441/quantification-of-sugars-and-organic-acids-in-biological-matrices-using-gc-qqq-ms
#12
Nirupama Samanmalie Jayasinghe, Himasha Mendis, Ute Roessner, Daniel Anthony Dias
Gas chromatography coupled with triple quadrupole mass spectrometry (GC-QqQ-MS) can be used to accurately quantify endogenous small molecules extracted from biological samples such as plants and human fluids including sera and urine. In order to quantify primary metabolites typically from central carbon metabolism such as sugars from glycolysis and the pentose phosphate pathway; and organic acids involved in the tricarboxylic acid (TCA) cycle; polar endogenous metabolites must be extracted from the samples of interest, chemically derivatized and quantified against a linear calibration curve to a corresponding authentic standard...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29761062/glycosylceramide-modifies-the-flavor-and-metabolic-characteristics-of-sake-yeast
#13
Jannatul Ferdouse, Yuki Yamamoto, Seiga Taguchi, Yumiko Yoshizaki, Kazunori Takamine, Hiroshi Kitagaki
In the manufacture of sake, Japanese traditional rice wine, sake yeast is fermented with koji, which is steamed rice fermented with the non-pathogenic fungus Aspergillus oryzae . During fermentation, sake yeast requires lipids, such as unsaturated fatty acids and sterols, in addition to substances provided by koji enzymes for fermentation. However, the role of sphingolipids on the brewing characteristics of sake yeast has not been studied. In this study, we revealed that glycosylceramide, one of the sphingolipids abundant in koji, affects yeast fermentation...
2018: PeerJ
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#14
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29755589/engineering-and-systems-level-analysis-of-pseudomonas-chlororaphis-for-production-of-phenazine-1-carboxamide-using-glycerol-as-the-cost-effective-carbon-source
#15
Ruilian Yao, Keli Pan, Huasong Peng, Lei Feng, Hongbo Hu, Xuehong Zhang
Background: Glycerol, an inevitable byproduct of biodiesel, has become an attractive feedstock for the production of value-added chemicals due to its availability and low price. Pseudomonas chlororaphis HT66 can use glycerol to synthesize phenazine-1-carboxamide (PCN), a phenazine derivative, which is strongly antagonistic to fungal phytopathogens. A systematic understanding of underlying mechanisms for the PCN overproduction will be important for the further improvement and industrialization...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29753190/what-makes-a-guillouiae-sfc-500-1a-able-to-co-metabolize-phenol-and-cr-vi-a-proteomic-approach
#16
Ornella Mailén Ontañon, Claudia Landi, Alfonso Carleo, Assunta Gagliardi, Laura Bianchi, Paola Solange González, Elizabeth Agostini, Luca Bini
Acinetobacter guillouiae SFC 500-1A is an environmental bacterium able to efficiently co-remediate phenol and Cr(VI). To further understand the molecular mechanisms triggered in this strain during the bioremediation process, variations in the proteomic profile after treatment with phenol and phenol plus Cr(VI) were evaluated. The proteomic analysis revealed the induction of the β-ketoadipate pathway for phenol oxidation and the assimilation of degradation products through TCA cycle and glyoxylate shunt. Phenol exposure increased the abundance of proteins associated to energetic processes and ATP synthesis, but it also triggered cellular stress...
April 27, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29753070/iterative-algorithm-guided-design-of-massive-strain-libraries-applied-to-itaconic-acid-production-in-yeast
#17
Eric M Young, Zheng Zhao, Bianca E M Gielesen, Liang Wu, D Benjamin Gordon, Johannes A Roubos, Christopher A Voigt
Metabolic engineering requires multiple rounds of strain construction to evaluate alternative pathways and enzyme concentrations. Optimizing multigene pathways stepwise or by randomly selecting enzymes and expression levels is inefficient. Here, we apply methods from design of experiments (DOE) to guide the construction of strain libraries from which the maximum information can be extracted without sampling every possible combination. We use Saccharomyces cerevisiae as a host for a novel six-gene pathway to itaconic acid, selected by comparing alternative shunt pathways that bypass the mitochondrial TCA cycle...
May 9, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29753025/identification-and-efficacy-of-glycine-serine-and-threonine-metabolism-in-potentiating-kanamycin-mediated-killing-of-edwardsiella-piscicida
#18
Jin-Zhou Ye, Xiang-Min Lin, Zhi-Xue Cheng, Yu-Bin Su, Wan-Xin Li, Far-Man Ali, Jun Zheng, Bo Peng
We previously showed that glucose potentiated kanamycin to kill multidrug-resistant Edwardsiella piscicida through activation of the TCA cycle. However, whether other regulatory mechanism is involved requires further investigation. By quantitative proteomics technology, iTRAQ, we systematically mapped the altered proteins in the presence of glucose and identified 94 differentially expressed proteins. The analysis of the altered proteins by pathways, amino acid biosynthesis and metabolism were enriched. And the most significantly altered eight amino acids tyrosine, phenylalanine, valine, leucine, isoleucine, glycine, serine and threonine were investigated for their potentiation of kanamycin to kill EIB202, where glycine, serine and threonine showed the strongest efficacy than the others...
May 9, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29752936/evidence-for-functional-and-regulatory-cross-talk-between-the-tricarboxylic-acid-cycle-2-oxoglutarate-dehydrogenase-complex-and-2-oxoadipate-dehydrogenase-on-the-l-lysine-l-hydroxylysine-and-l-tryptophan-degradation-pathways-from-studies-in-vitro
#19
Natalia S Nemeria, Gary Gerfen, Luying Yang, Xu Zhang, Frank Jordan
Herein are reported findings in vitro suggesting both functional and regulatory cross-talk between the human 2-oxoglutarate dehydrogenase complex (hOGDHc), a key regulatory enzyme within the tricarboxylic acid cycle (TCA cycle), and a novel 2-oxoadipate dehydrogenase complex (hOADHc) from the final degradation pathway of l-lysine, l-hydroxylysine and l-tryptophan. The following could be concluded from our studies by using hOGDHc and hOADHc assembled from their individually expressed components in vitro: (i) Different substrate preferences (kcat /Km ) were displayed by the two complexes even though they share the same dihydrolipoyl succinyltransferase (hE2o) and dihydrolipoyl dehydrogenase (hE3) components; (ii) Different binding modes were in evidence for the binary hE1o-hE2o and hE1a-hE2o subcomplexes according to fluorescence titrations using site-specifically labeled hE2o-derived proteins; (iii) Similarly to hE1o, the hE1a also forms the ThDP-enamine radical from 2-oxoadipate (electron paramagnetic resonance detection) in the oxidative half reaction; (iv) Both complexes produced superoxide/H2 O2 from O2 in the reductive half reaction suggesting that hE1o, and hE1a (within their complexes) could both be sources of reactive oxygen species generation in mitochondria from 2-oxoglutarate and 2-oxoadipate, respectively; (v) Based on our findings, we speculate that hE2o can serve as a trans-glutarylase, in addition to being a trans-succinylase, a role suggested by others; (vi) The glutaryl-CoA produced by hOADHc inhibits hE1o, as does succinyl-CoA, suggesting a regulatory cross-talk between the two complexes on the different metabolic pathways...
May 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29752600/pancreatic-cancer-metabolism-molecular-mechanisms-and-clinical-applications
#20
REVIEW
Abdel Nasser Hosein, Muhammad Shaalan Beg
PURPOSE OF REVIEW: Pancreatic adenocarcinoma is a leading cause of cancer mortality in western countries with a uniformly poor prognosis. Unfortunately, there has been little in the way of novel therapeutics for this malignancy over the last several decades. Derangements in metabolic circuitry favoring excess glycolysis are increasingly recognized as a key hallmark of cancer. RECENT FINDINGS: The role of alterations in glutamine metabolism in pancreatic tumor progression has been elucidated in animal models and human cells lines, and there has been considerable interest in exploiting these aberrations for the treatment of pancreatic cancer...
May 11, 2018: Current Oncology Reports
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