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https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#1
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427419/tnf-%C3%AE-promotes-extracellular-vesicle-release-in-mouse-astrocytes-through-glutaminase
#2
Kaizhe Wang, Ling Ye, Hongfang Lu, Huili Chen, Yanyan Zhang, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown...
April 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28426698/extensive-alterations-of-blood-metabolites-in-pediatric-cerebral-malaria
#3
Sanchit Gupta, Karl Seydel, Miguel A Miranda-Roman, Catherine M Feintuch, Alex Saidi, Ryung S Kim, Gretchen L Birbeck, Terrie Taylor, Johanna P Daily
Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy...
2017: PloS One
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#4
Jiaqiu Li, Ping Song, Liyuan Zhu, Neelum Aziz, Qiyin Zhou, Yulong Zhang, Wenxia Xu, Lifeng Feng, Dingwei Chen, Xian Wang, Hongchuan Jin
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420467/-study-of-plasma-amino-acid-related-metabolites-of-septic-rats-using-gas-chromatography-mass-spectrometry
#5
Jin Su, Yimin Zhu, Yu Jiang, Lianhong Zou, Xiaoliang Liu, Yixiao Xu
OBJECTIVE: To reveal the pathophysiological changes of sepsis, the plasma metabonomics of septic rats was determined and differential metabolites were determined by gas chromatography-mass spectrometry (GC-MS). METHODS: Male Spraguee-Dawley (SD) rats about 8 weeks were randomly divided into sham group (n = 18) and sepsis group (n = 24). Cecal ligation and puncture (CLP) was used to build sepsis model, while cecum was kept intact only in the sham group. 6 hours after the operation, rats were anesthetized, and blood was harvested through heart thoracotomy...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28419115/properties-of-the-cuticular-proteins-of-anopheles-gambiae-as-revealed-by-serial-extraction-of-adults
#6
Yihong Zhou, Majors J Badgett, Lynne Billard, John Hunter Bowen, Ron Orlando, Judith H Willis
How cuticular proteins (CPs) interact with chitin and with each other in the cuticle remains unresolved. We employed LC-MS/MS to identify CPs from 5-6 day-old adults of Anopheles gambiae released after serial extraction with PBS, EDTA, 2-8M urea, and SDS as well as those that remained unextracted. Results were compared to published data on time of transcript abundance, localization of proteins within structures and within the cuticle, as well as properties of individual proteins, length, pI, percent histidine, tyrosine, glutamine, and number of AAP[A/V/L] repeats...
2017: PloS One
https://www.readbyqxmd.com/read/28414307/metabolic-inhibitors-accentuate-the-anti-tumoral-effect-of-hdac5-inhibition
#7
E Hendrick, P Peixoto, A Blomme, C Polese, N Matheus, J Cimino, A Frère, A Mouithys-Mickalad, D Serteyn, L Bettendorff, B Elmoualij, P De Tullio, G Eppe, F Dequiedt, V Castronovo, D Mottet
The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has firmly laid the cancer community to explore HDAC inhibition as a therapeutic approach for cancer treatment. Hitting one HDAC member could yield clinical benefit but this required a complete understanding of the functions of the different HDAC members. Here we explored the consequences of specific HDAC5 inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron-dependent reactive oxygen species (ROS) production, ultimately leading to apoptotic cell death as well as mechanisms of mitochondria quality control (mitophagy and mitobiogenesis)...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28407895/test-for-l-glutamate-inhibition-of-growth-of-alternaria-alternata-by-inducing-resistance-in-tomato-fruit
#8
Jiali Yang, Cui Sun, Da Fu, Ting Yu
Although numerous studies have reported the involvement of glutamate in plant abiotic stress, relatively little is known about the role of glutamate in plant defence against pathogens. To gain further knowledge, we investigated the effect of glutamate on Alternaria alternata in tomato fruit. A multidisciplinary approach was pursued, combining exogenous glutamate applications, enzymatic activity measurements and real-time quantitative PCR analysis. The results showed glutamate significantly reduced the disease incidence in tomato caused by A...
September 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28400476/gad1-upregulation-programs-aggressive-features-of-cancer-cell-metabolism-in-the-brain-metastatic-microenvironment
#9
Patricia M Schnepp, Dennis D Lee, Ian H Guldner, Treasa K O'Tighearnaigh, Erin N Howe, Bhavana Palakurthi, Kaitlyn E Eckert, Tiffany A Toni, Brandon L Ashfeld, Siyuan Zhang
The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downegulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells...
April 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28398002/alpha-ketoglutarate-curbs-differentiation-and-induces-cell-death-in-mesenchymal-stromal-precursors-with-mitochondrial-dysfunction
#10
Karmveer Singh, Linda Krug, Abhijit Basu, Patrick Meyer, Nicolai Treiber, Seppe Vander Beken, Meinhard Wlaschek, Stefan Kochanek, Wilhelm Bloch, Hartmut Geiger, Pallab Maity, Karin Scharffetter-Kochanek
Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. We here demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape...
April 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28393748/gut-microbiota-of-mice-putatively-modifies-amino-acid-metabolism-in-the-host-brain
#11
Takahiro Kawase, Mao Nagasawa, Hiromi Ikeda, Shinobu Yasuo, Yasuhiro Koga, Mitsuhiro Furuse
Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age...
April 10, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28389772/anoxybacillus-sp-strain-uark-01-a-new-thermophilic-soil-bacterium-with-hyperthermostable-alkaline-laccase-activity
#12
Thamir H Al-Kahem Al-Balawi, Adam L Wood, Alexis Solis, Ted Cooper, Ravi D Barabote
We describe the isolation and characteristics of a novel thermophilic bacterium from soil. The organism is a member of the Anoxybacillus genus based on phylogenetic analysis of the 16S rRNA gene. The 16S rRNA of the organism shares >99% sequence identity with those of two species, Anoxybacillus rupiensis and A. geothermalis. We named this isolate as Anoxybacillus sp. strain UARK-01. UARK-01 grows optimally in the presence of oxygen at 55 °C and pH 8. It grew excellently in the presence of lignin as the sole carbon source...
April 8, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28386552/l-glutamine-supplementation-alleviates-constipation-during-late-gestation-of-mini-sows-by-modifying-the-microbiota-composition-in-feces
#13
Yuanyuan Zhang, Taofeng Lu, Lingxia Han, Lili Zhao, Yinjie Niu, Hongyan Chen
Constipation occurs frequently in both sows and humans, particularly, during late gestation. The microbial community of the porcine gut, the enteric microbiota, plays a critical role in functions that sustain intestinal health. Hence, microbial regulation during pregnancy may be important to prevent host constipation. The present study was conducted to determine whether L-glutamine (Gln) supplementation improved intestinal function and alleviated constipation by regulation of enteric microbiota. 16S rRNA sequences obtained from fecal samples from 9 constipated sows (3 in the constipation group and 6 in the 1...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28380531/effect-of-abomasal-butyrate-infusion-on-gene-expression-in-the-duodenum-of-lambs
#14
A P Foote, C M Zarek, L A Kuehn, H C Cunningham, K M Cammack, H C Freetly, A K Lindholm-Perry
A previous study infusing butyrate into the abomasum of sheep produced increased oxygen, glucose, glutamate, and glutamine uptake by the portal-drained viscera. These changes were thought to be partially due to increases in glycolysis and cell proliferation. The purpose of this study was to evaluate the duodenum transcriptome of control and butyrate-treated lambs to determine whether genes involved in these pathways were altered. Polled Dorset lambs ( = 9) received a pulse dose of either butyrate (10 mg/kg BW) or an equal volume of a buffered saline solution (1 mL/kg BW) daily at the time of feeding...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28374265/both-high-and-low-plasma-glutamine-levels-predict-mortality-in-critically-ill-patients
#15
Takae Tsujimoto, Kentaro Shimizu, Nobuaki Hata, Tatsuya Takagi, Etsuko Uejima, Hiroshi Ogura, Masafumi Wasa, Takeshi Shimazu
PURPOSE: Plasma amino acids are important indicators for understanding human kinetics and amino acid dynamics. We aimed to investigate the association between the plasma glutamine levels and the mortality rates and determine whether plasma glutamine can predict the prognosis of critically ill patients. METHODS: The clinical records of adult patients who were admitted to an ICU were retrospectively evaluated to investigate the plasma levels of amino acids, including glutamine...
April 3, 2017: Surgery Today
https://www.readbyqxmd.com/read/28372177/hydrophilic-interaction-chromatography-and-evaporative-light-scattering-detection-for-the-determination-of-polar-analytes-in-belgian-endive
#16
Carlo Annaratone, Ans De Roeck, Maarten L A T M Hertog, Bart M Nicolaï
Belgian endive (Cichorium intybus L. var. foliosum Hegi), a popular produce in northern Europe, has been thoroughly studied in regard to its bitter sesquiterpene lactones content. Much less is known about on its sweetness and crunchiness, which are typically linked to the content of polar compounds such as sugars, organic acids and salts. Through HILIC-HPLC-MS, it was shown that simple sugars, amino acids, and potassium chloride are abundant in Belgian endive extracts. Subsequently, a HILIC-HPLC-ELSD method for the analysis of such compounds with run times below six minutes was developed...
August 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28368337/crispr-cas9-mediated-gene-silencing-of-the-mutant-huntingtin-gene-in-an-in-vitro-model-of-huntington-s-disease
#17
Nivya Kolli, Ming Lu, Panchanan Maiti, Julien Rossignol, Gray L Dunbar
Huntington's disease (HD) is a fatal neurodegenerative genetic disease characterized by a loss of neurons in the striatum. It is caused by a mutation in the Huntingtin gene (HTT) that codes for the protein huntingtin (HTT). The mutant Huntingtin gene (mHTT) contains extra poly-glutamine (CAG) repeats from which the translated mutant huntingtin proteins (mHTT) undergo inappropriate post-translational modifications, conferring a toxic gain of function, in addition to its non-functional property. In order to curb the production of the mHTT, we have constructed two CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR associate protein) plasmids, among which one nicks the DNA at untranslated region upstream to the open reading frame (uORF), and the other nicks the DNA at exon1-intron boundary...
April 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28365292/evolving-transpeptidase-and-hydrolytic-variants-of-%C3%AE-glutamyl-transpeptidase-from-bacillus-licheniformis-by-targeted-mutations-of-conserved-residue-arg109-and-their-biotechnological-relevance
#18
Shruti Bindal, Sujata Sharma, Tej P Singh, Rani Gupta
γ-Glutamyl transpeptidase (GGT) catalyzes the transfer of the γ-glutamyl moiety from donor compounds such as l-glutamine (Gln) and glutathione (GSH) to an acceptor. During the biosynthesis of various γ-glutamyl-containing compounds using GGT enzyme, auto-transpeptidation reaction leads to the formation of unwanted byproducts. Therefore, in order to alter the auto-transpeptidase activity of the GGT enzyme, the binding affinity of Gln should be modified. Structural studies of the Bacillus licheniformis GGT (BlGT) complexed with the glutamic acid has shown that glutamic acid has strong ionic interactions through its α-carboxlic group with the guanidine moiety of Arg109...
March 30, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28363111/3t-hippocampal-glutamate-glutamine-complex-reflects-verbal-memory-decline-in-aging
#19
Simona Nikolova, Shauna M Stark, Craig E L Stark
The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and glutamate-glutamine levels using short echo time magnetic resonance spectroscopy. Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word-recall task, and resting-state functional connectivity. While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28358347/the-enzymology-of-2-hydroxyglutarate-2-hydroxyglutaramate-and-2-hydroxysuccinamate-and-their-relationship-to-oncometabolites
#20
Vivek A Hariharan, Travis T Denton, Sarah Paraszcszak, Kyle McEvoy, Thomas M Jeitner, Boris F Krasnikov, Arthur J L Cooper
Many enzymes make "mistakes". Consequently, repair enzymes have evolved to correct these mistakes. For example, lactate dehydrogenase (LDH) and mitochondrial malate dehydrogenase (mMDH) slowly catalyze the reduction of 2-oxoglutarate (2-OG) to the oncometabolite l-2-hydroxyglutarate (l-2-HG). l-2-HG dehydrogenase corrects this error by converting l-2-HG to 2-OG. LDH also catalyzes the reduction of the oxo group of 2-oxoglutaramate (2-OGM; transamination product of l-glutamine). We show here that human glutamine synthetase (GS) catalyzes the amidation of the terminal carboxyl of both the l- and d- isomers of 2-HG...
March 30, 2017: Biology
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