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https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#1
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28218241/massively-augmented-hippocampal-dentate-granule-cell-activation-accompanies-epilepsy-development
#2
Christopher G Dengler, Cuiyong Yue, Hajime Takano, Douglas A Coulter
In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218035/microrna-153-regulates-glutamine-metabolism-in-glioblastoma-through-targeting-glutaminase
#3
Zhenyang Liu, Junyu Wang, Yunjun Li, Juan Fan, Lihua Chen, Ruxiang Xu
Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28212626/a-global-characterization-of-the-translational-and-transcriptional-programs-induced-by-methionine-restriction-through-ribosome-profiling-and-rna-seq
#4
Ke Zou, Qi Ouyang, Hao Li, Jiashun Zheng
BACKGROUND: Among twenty amino acids, methionine has a special role as it is coded by the translation initiation codon and methionyl-tRNAi (Met-tRNAi) is required for the assembly of the translation initiation complex. Thus methionine may play a special role in global gene regulation. Methionine has also been known to play important roles in cell growth, development, cancer, and aging. In this work, we characterize the translational and transcriptional programs induced by methionine restriction (MetR) and investigate the potential mechanisms through which methionine regulates gene expression, using the budding yeast S...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28212609/exogenous-glutamate-rapidly-induces-the-expression-of-genes-involved-in-metabolism-and-defense-responses-in-rice-roots
#5
Chia-Cheng Kan, Tsui-Yun Chung, Hsin-Yu Wu, Yan-An Juo, Ming-Hsiun Hsieh
BACKGROUND: Glutamate is an active amino acid. In addition to protein synthesis and metabolism, increasing evidence indicates that glutamate may also function as a signaling molecule in plants. Still, little is known about the nutritional role of glutamate and genes that are directly regulated by glutamate in rice. RESULTS: Exogenous glutamate could serve as a nitrogen nutrient to support the growth of rice seedlings, but it was not as effective as ammonium nitrate or glutamine...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#6
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#7
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28206740/d-amino-acid-levels-in-perfused-mouse-brain-tissue-and-blood-a-comparative-study
#8
Choyce A Weatherly, Siqi Du, Curran Parpia, Polan T Santos, Adam L Hartman, Daniel W Armstrong
The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels...
February 16, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28202761/the-long-noncoding-rna-neat1-exerts-anti-hantaviral-effects-by-acting-as-a-positive-feedback-for-rig-i-signaling
#9
Hongwei Ma, Peijun Han, Wei Ye, Hesong Chen, Xuyang Zheng, Linfeng Cheng, Liang Zhang, Lan Yu, Xing'an Wu, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA, NEAT1, as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28197753/asparaginase-pharmacology-challenges-still-to-be-faced
#10
REVIEW
Claudia Lanvers-Kaminsky
PURPOSE: The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated. METHODS: We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo...
February 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28192215/review-of-metabolic-pathways-activated-in-cancer-cells-as-determined-through-isotopic-labeling-and-network-analysis
#11
Wentao Dong, Mark A Keibler, Gregory Stephanopoulos
Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism...
February 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28186970/high-expression-of-gfat1-predicts-unfavorable-prognosis-in-patients-with-hepatocellular-carcinoma
#12
Lili Li, Miaomiao Shao, Peike Peng, Caiting Yang, Shushu Song, Fangfang Duan, Dongwei Jia, Mingming Zhang, Junjie Zhao, Ran Zhao, Weicheng Wu, Lan Wang, Can Li, Hao Wu, Jie Zhang, Xin Wu, Yuanyuan Ruan, Jianxin Gu
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. As a branch of glucose metabolism, hexosamine biosynthesis pathway (HBP) has been reported to play a critical role in the insulin resistance and progression of cancer. Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting enzyme of the HBP; nevertheless, the prognostic value of GFAT1 in HCC remains elusive. In this study, we found that high expression of GFAT1 was significantly associated with serum alpha-fetoprotein (AFP), serum alanine aminotransferase (ALT), tumor size, tumor encapsulation, T stage and TNM stage...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182739/distinct-effects-of-endosomal-escape-and-inhibition-of-endosomal-trafficking-on-gene-delivery-via-electrotransfection
#13
Lisa D Cervia, Chun-Chi Chang, Liangli Wang, Fan Yuan
A recent theory suggests that endocytosis is involved in uptake and intracellular transport of electrotransfected plasmid DNA (pDNA). The goal of the current study was to understand if approaches used previously to improve endocytosis of gene delivery vectors could be applied to enhancing electrotransfection efficiency (eTE). Results from the study showed that photochemically induced endosomal escape, which could increase poly-L-lysine (PLL)-mediated gene delivery, decreased eTE. The decrease could not be blocked by treatment of cells with endonuclease inhibitors (aurintricarboxylic acid and zinc ion) or antioxidants (L-glutamine and ascorbic acid)...
2017: PloS One
https://www.readbyqxmd.com/read/28179423/xanthine-dehydrogenase-1-silencing-in-aedes-aegypti-mosquitoes-promotes-a-blood-feeding-induced-adulticidal-activity
#14
Jun Isoe, Natthida Petchampai, Yurika E Isoe, Katrina Co, Stacy Mazzalupo, Patricia Y Scaraffia
Aedesaegypti has 2 genes encoding xanthine dehydrogenase (XDH). We analyzed XDH1 and XDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injecting double-stranded RNA (dsRNA) against XDH1, XDH2, or both. Disruption of XDH by allopurinol or XDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, and reproduction...
February 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28170216/proteins-containing-expanded-polyglutamine-tracts-and-neurodegenerative-disease
#15
Adewale Adegbuyiro, Faezeh Sedighi, Albert W Pilkington, Sharon Groover, Justin Legleiter
Several hereditary neurological and neuromuscular diseases are caused by an abnormal expansion of trinucleotide repeats. To date, there have been 10 of these trinucleotide repeat disorders associated with an expansion of the codon CAG encoding glutamine (Q). For these polyglutamine (polyQ) diseases, there is a critical threshold length of the CAG repeat required for disease, and further expansion beyond this threshold is correlated with age of onset and symptom severity. PolyQ expansion in the translated proteins promotes their self-assembly into a variety of oligomeric and fibrillar aggregate species that accumulate into the hallmark proteinaceous inclusion bodies associated with each disease...
February 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28162896/haploinsufficiency-of-sirt1-enhances-glutamine-metabolism-and-promotes-cancer-development
#16
Natalie S X Ren, Ming Ji, Erik J Tokar, Evan L Busch, Xiaojiang Xu, DeAsia Lewis, Xiangchun Li, Aiwen Jin, Yanping Zhang, William K K Wu, Weichun Huang, Leping Li, David C Fargo, Temitope O Keku, Robert S Sandler, Xiaoling Li
SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, plays a vital role in the regulation of metabolism, stress responses, and genome stability. However, the role of SIRT1 in the multi-step process leading to transformation and/or tumorigenesis, as either a tumor suppressor or tumor promoter, is complex and may be dependent upon the context in which SIRT1 activity is altered, and the role of SIRT1 in tumor metabolism is unknown. Here, we demonstrate that SIRT1 dose-dependently regulates cellular glutamine metabolism and apoptosis, which in turn differentially impact cell proliferation and cancer development...
February 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28158936/characteristic-nh3-and-co-losses-of-sodiated-peptides-c-terminated-by-glutamine-residue
#17
Xinshu Guan, Bing Wang, Huixin Wang, Jinrong Liu, Ying Li, Xinhua Guo
RATIONALE: In certain conditions some amino acid (AA) residues undergo special reactions in the gas phase, generating characteristic neutral losses and product ions. Taking these special fragments into account and understanding the effect of AA residues on peptide cleavages will consummate database search algorithms and manual data interpretation in peptide sequencing by mass spectrometry (MS). In this study, the detail of the characteristic NH3 and CO losses of glutamine (Gln) residue located at the C-terminus of peptides is presented...
February 3, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28149015/role-of-bioflavonoid-quercetin-on-expression-of-urea-cycle-enzymes-astrocytic-and-inflammatory-markers-in-hyperammonemic-rats
#18
Sivamani Kanimozhi, Perumal Subramanian, Sakkaravarthy Shanmugapriya, Subramanian Sathishkumar
This study evaluates the role of quercetin on the expression of urea cycle enzymes, astrocytic, neuronal and inflammatory markers in hyperammonemic rats. Hyperammonemia (provoked by intraperitonial injections of (ammonium chloride-100 mg/kg b.w for 56 days), showed diminished expression of urea cycle enzymes [carbamyl phosphate synthetase-1 (CPS-1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS) and arginase (ARG)] in liver and decreased expression of neuronal and astrocytic markers-glutamine synthase (GS) and phosphate activated glutaminase (PAG) in brain and increased expression of brain inflammatory markers such as interleukin 6 (IL6), inducible nitric oxide synthase (iNOS) and nuclear transcription factor kappa B (NF-κB) (by western blot analysis) and exhibited downregulated expression of soluble guanylate cyclase (sGC), glial fibrillary acidic protein (GFAP) in brain and ASS in liver investigated (by RT-PCR)...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28139777/isolation-and-characterization-of-a-spotted-leaf-32-mutant-with-early-leaf-senescence-and-enhanced-defense-response-in-rice
#19
Liting Sun, Yihua Wang, Ling-Long Liu, Chunming Wang, Ting Gan, Zhengyao Zhang, Yunlong Wang, Di Wang, Mei Niu, Wuhua Long, Xiaohui Li, Ming Zheng, Ling Jiang, Jianmin Wan
Leaf senescence is a complex biological process and defense responses play vital role for rice development, their molecular mechanisms, however, remain elusive in rice. We herein reported a rice mutant spotted leaf 32 (spl32) derived from a rice cultivar 9311 by radiation. The spl32 plants displayed early leaf senescence, identified by disintegration of chloroplasts as cellular evidence, dramatically decreased contents of chlorophyll, up-regulation of superoxide dismutase enzyme activity and malondialdehyde, as physiological characteristic, and both up-regulation of senescence-induced STAY GREEN gene and senescence-associated transcription factors, and down-regulation of photosynthesis-associated genes, as molecular indicators...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139703/the-differential-ability-of-asparagine-and-glutamine-in-promoting-the-closed-active-enzyme-conformation-rationalizes-the-wolinella-succinogenes-l-asparaginase-substrate-specificity
#20
Hien Anh Nguyen, Donald L Durden, Arnon Lavie
Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase activity in contrast to Uniprot entry P50286 (WoA-S121) that has a serine residue at this position. Towards understanding how this residue impacts the L-glutaminase property, kinetic analysis was coupled with crystal structure determination of these WoA variants...
January 31, 2017: Scientific Reports
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