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amino acid starvation

H Edward Wong, Chung-Jr Huang, Zhongqi Zhang
Elevated amino acid misincorporation levels during protein translation can cause disease and adversely impact biopharmaceutical product quality. Our previous work, along with that of others, identified numerous low-level unintended sequence variants. However, due to the limited analytical detection efficiency, we believed that these observations represented only a fraction of biologically relevant outcomes. Since amino acid misincorporation can be exacerbated by amino acid starvation, we believed that a more comprehensive set of sequence variants could be derived through systematic starvation...
November 12, 2018: Biochemistry
Fabian Classen, Philip Kranz, Helena Riffkin, Mosche Pompsch, Alexandra Wolf, Kirsten Göpelt, Melanie Baumann, Jennifer Baumann, Ulf Brockmeier, Eric Metzen
Autophagy is commonly described as a cell survival mechanism and has been implicated in chemo- and radioresistance of cancer cells. Whether ionizing radiation induced autophagy triggers tumor cell survival or cell death still remains unclear. In this study the autophagy related proteins Beclin1 and ATG7 were tested as potential targets to sensitize colorectal carcinoma cells to ionizing radiation under normoxic, hypoxic and starvation conditions. Colony formation, apoptosis and cell cycle analysis revealed that knockdown of Beclin1 or ATG7 does not enhance radiosensitivity in HCT-116 cells...
November 6, 2018: Experimental Cell Research
Jeong-Mok Kim, Ok-Hee Seok, Shinyeong Ju, Ji-Eun Heo, Jeonghun Yeom, Da-Som Kim, Joo-Yeon Yoo, Alexander Varshavsky, Cheolju Lee, Cheol-Sang Hwang
In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids...
November 8, 2018: Science
Cecilia Picazo, Emilia Matallana, Agustín Aranda
The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation...
November 7, 2018: Scientific Reports
Bethany Hart, Elizabeth Morgan, Emilyn Alejandro
Fetal growth restriction is one of the most common obstetrical complications resulting in significant perinatal morbidity and mortality. The most frequent etiology of human singleton fetal growth restriction is placental insufficiency, which occurs secondary to reduced utero-placental perfusion, abnormal placentation, impaired trophoblast invasion and spiral artery remodeling, resulting in altered nutrient and oxygen transport. Two nutrient-sensing proteins involved in placental development and glucose and amino acid transport are mechanistic target of rapamycin (mTOR) and O-linked N-acetylglucosamine transferase (OGT), which are both regulated by availability of oxygen...
October 1, 2018: Journal of Molecular Endocrinology
Marcel Naumann, Hans-Michael Hubberten, Mutsumi Watanabe, Robert Hänsch, Mark Aurel Schöttler, Rainer Hoefgen
Sulfite reductase (SIR) is a key enzyme in higher plants in the assimilatory sulfate reduction pathway. SIR, being exclusively localized in plastids, catalyzes the reduction of sulfite (SO3 2- ) to sulfide (S2- ) and is essential for plant life. We characterized transgenic plants leading to co-suppression of the SIR gene in tobacco ( Nicotiana tabacum cv. Samsun NN). Co-suppression resulted in reduced but not completely extinguished expression of SIR and in a reduction of SIR activity to about 20-50% of the activity in control plants...
2018: Frontiers in Plant Science
Naveen C Joshi, Andreas J Meyer, Sajid A K Bangash, Zhi-Liang Zheng, Thomas Leustek
γ-Glutamylcyclotransferase initiates glutathione degradation to component amino acids l-glutamate, l-cysteine and l-glycine. The enzyme is encoded by three genes in Arabidopsis thaliana, one of which (GGCT2;1) is transcriptionally upregulated by starvation for the essential macronutrient sulfur (S). Regulation by S-starvation suggests that GGCT2;1 mobilizes l-cysteine from glutathione when there is insufficient sulfate for de novo l-cysteine synthesis. The response of wild-type seedlings to S-starvation was compared to ggct2;1 null mutants...
October 10, 2018: New Phytologist
Nanbiao Long, Thomas Orasch, Shizhu Zhang, Lu Gao, Xiaoling Xu, Peter Hortschansky, Jing Ye, Fenli Zhang, Kai Xu, Fabio Gsaller, Maria Straßburger, Ulrike Binder, Thorsten Heinekamp, Axel A Brakhage, Hubertus Haas, Ling Lu
Both branched-chain amino acids (BCAA) and iron are essential nutrients for eukaryotic cells. Previously, the Zn2Cys6-type transcription factor Leu3/LeuB was shown to play a crucial role in regulation of BCAA biosynthesis and nitrogen metabolism in Saccharomyces cerevisiae and Aspergillus nidulans. In this study, we found that the A. fumigatus homolog LeuB is involved in regulation of not only BCAA biosynthesis and nitrogen metabolism but also iron acquisition including siderophore metabolism. Lack of LeuB caused a growth defect, which was cured by supplementation with leucine or iron...
October 2018: PLoS Genetics
Manuel Becana, Stefanie Wienkoop, Manuel A Matamoros
Sulfur is an essential nutrient in plants as a constituent element of some amino acids, metal cofactors, coenzymes, and secondary metabolites. Not surprisingly, sulfur deficiency decreases plant growth, photosynthesis, and seed yield in both legumes and non-legumes. In nodulated legumes, sulfur supply is positively linked to symbiotic nitrogen fixation (SNF) and sulfur starvation causes three additional major effects: decrease of nodulation, inhibition of SNF, and slowing down of nodule metabolism. These effects are due, at least in part, to the impairment of nitrogenase biosynthesis and activity, the accumulation of nitrogen-rich amino acids, and the decline in leghemoglobin, ferredoxin, ATP, and glucose in nodules...
2018: Frontiers in Plant Science
Natalie M Izral, Robert B Brua, Joseph M Culp, Adam G Yates
There is a need to develop bioassessment tools that can diagnose the effects of individual stressors that can have multiple ecological effects. Using nuclear magnetic resonance (NMR)-based metabolomics, our experiments aimed to identify the sensitivity of metabolites to changes in food availability and dissolved oxygen (DO) concentrations, and compare these results to identify metabolites that may differentiate between the effects of these two stressors. Forty-eight, laboratory-raised, red swamp crayfish (Procambarus clarkii) were randomly assigned and exposed to one of three food availability or DO treatment levels (high, normal, low)...
October 25, 2018: Environmental Science and Pollution Research International
Myles Levey, Stefan Timm, Tabea Mettler-Altmann, Gian Luca Borghi, Maria Koczor, Stéphanie Arrivault, Andreas Pm Weber, Hermann Bauwe, Udo Gowik, Peter Westhoff
Photorespiration is indispensable for oxygenic photosynthesis since it detoxifies and recycles 2-phosphoglycolate (2PG), which is the primary oxygenation product of Rubisco. However, C4 plant species typically display very low rates of photorespiration due to their efficient biochemical carbon concentrating mechanism. Thus, the broader relevance of photorespiration in these organisms remains unclear. In this study, we assessed the importance of a functional photorespiratory pathway in the C4 plant Flaveria bidentis using a knockdown of the first enzymatic step, namely, 2PG phosphatase (PGLP)...
October 23, 2018: Journal of Experimental Botany
Adhish S Walvekar, Rajalakshmi Srinivasan, Ritu Gupta, Sunil Laxman
Methionine availability during overall amino acid limitation metabolically reprograms cells to support proliferation, the underlying basis for which remains unclear. Here, we construct the organization of this methionine mediated anabolic program, using yeast. Combining comparative transcriptome analysis, biochemical and metabolic flux based approaches, we discover that methionine rewires overall metabolic outputs by increasing the activity of a key regulatory node. This comprises of: the pentose phosphate pathway (PPP) coupled with reductive biosynthesis, the glutamate dehydrogenase (GDH) dependent synthesis of glutamate/glutamine, and pyridoxal-5-phosphate (PLP) dependent transamination capacity...
October 24, 2018: Molecular Biology of the Cell
Shuqian Tan, Aomei Li, Yang Wang, Shi Wangpeng
BACKGROUND: The Neuropeptide F (NPF) is an intercellular signaling molecule that mediates many physiological and behavioral processes. However, the function of neuropeptide F in mediating the feeding behavior of Locusta migratoria has been unclear. RESULTS: The neuropeptide F 1 precursor cDNA from L. migratoria was obtained and analyzed, and its amino acid sequence deduced. Mature LmiNPF1 was composed of 36 amino acids and was similar to that of Schistocerca gregaria...
October 22, 2018: Pest Management Science
Qiang Guo, Yuki Yoshida, Ian T Major, Kun Wang, Koichi Sugimoto, George Kapali, Nathan E Havko, Christoph Benning, Gregg A Howe
Plant immune responses mediated by the hormone jasmonoyl-l-isoleucine (JA-Ile) are metabolically costly and often linked to reduced growth. Although it is known that JA-Ile activates defense responses by triggering the degradation of JASMONATE ZIM DOMAIN (JAZ) transcriptional repressor proteins, expansion of the JAZ gene family in vascular plants has hampered efforts to understand how this hormone impacts growth and other physiological tasks over the course of ontogeny. Here, we combined mutations within the 13-member Arabidopsis JAZ gene family to investigate the effects of chronic JAZ deficiency on growth, defense, and reproductive output...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Vittorio Emanuele Bianchi
The metabolic sources of energy for myocardial contractility include mainly free fatty acids (FFA) for 95%, and in lesser amounts for 5% from glucose and minimal contributions from other substrates such lactate, ketones, and amino acids. However, myocardial efficiency is influenced by metabolic condition, overload, and ischemia. During cardiac stress, cardiomyocytes increase glucose oxidation and reduce FFA oxidation. In patients with ischemic coronary disease and heart failure, the low oxygen availability limits myocardial reliance on FFA and glucose utilization must increase...
September 11, 2018: Current Problems in Cardiology
Siddharth Jayakumar, Shlesha Richhariya, Bipan Kumar Deb, Gaiti Hasan
Organisms need to co-ordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In Drosophila , growth occurs during larval development. Larvae are thus critically dependant on nutritional inputs but post critical weight they pupariate even when starved. How nutrient availability is coupled to the internal metabolic state for the decision to pupariate needs better understanding. We had earlier identified glutamatergic interneurons in the ventral ganglion that regulate pupariation on a protein-deficient diet...
October 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hallvard L Olsvik, Steingrim Svenning, Yakubu Princely Abudu, Andreas Brech, Harald Stenmark, Terje Johansen, Jakob Mejlvang
Starvation is a fundamental type of stress naturally occurring in biological systems. All organisms have therefore evolved different safeguard mechanisms to cope with deficiencies in various types of nutrients. Cells, from yeast to humans, typically respond to amino acid starvation by initiating degradation of cellular components by inducing autophagy. This degradation releases metabolic building blocks to sustain essential core cellular processes. Increasing evidence indicates that starvation-induced autophagy also acts to prepare cells for prolonged starvation by degrading key regulators of different cellular processes...
October 8, 2018: Autophagy
Deniz Gulfem Ozturk, Muhammed Kocak, Arzu Akcay, Kubilay Kinoglu, Erdogan Kara, Yalcin Buyuk, Hilal Kazan, Devrim Gozuacik
Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress response mechanism. Active at basal levels in eukaryotes, autophagy is upregulated under stress providing cells with building blocks such as amino acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to amino acid availability. Stress-mediated inhibition of MTORC1 results in the dephosphorylation and nuclear translocation of the TFE/MITF family of transcriptional factors, and triggers an autophagy- and lysosomal-related gene transcription program...
October 5, 2018: Autophagy
Gabriela Torres Cruvinel, Henrique Iglesias Neves, Beny Spira
Glyphosate, the most widely used herbicide in both agricultural and urban areas is toxic for plants and for many bacterial species. The mechanism of action of glyphosate is through the inhibition of the EPSP synthase, a key enzyme in the biosynthetic pathway of aromatic amino acids. Here we show that glyphosate induces the stringent response in Escherichia coli. Bacteria treated with glyphosate stop growing and accumulate ppGpp. Both growth arrest and ppGpp accumulation are restored to normal levels upon addition of aromatic amino acids...
October 4, 2018: Molecular Genetics and Genomics: MGG
Christin Lorenz, Saskia Brandt, Ljudmilla Borisjuk, Hardy Rolletschek, Nicolas Heinzel, Takayuki Tohge, Alisdair R Fernie, Hans-Peter Braun, Tatjana M Hildebrandt
The sulfur dioxygenase ETHE1 oxidizes persulfides in the mitochondrial matrix and is involved in the degradation of L-cysteine and hydrogen sulfide. ETHE1 has an essential but as yet undefined function in early embryo development of Arabidopsis thaliana . In leaves, ETHE1 is strongly induced by extended darkness and participates in the use of amino acids as alternative respiratory substrates during carbohydrate starvation. Thus, we tested the effect of darkness on seed development in an ETHE1 deficient mutant in comparison to the wild type...
2018: Frontiers in Plant Science
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