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https://www.readbyqxmd.com/read/29746817/arginine-inhibits-the-malignant-transformation-induced-by-interferon-gamma-through-the-nf-%C3%AE%C2%BAb-gcn2-eif2%C3%AE-signaling-pathway-in-mammary-epithelial-cells-in-vitro-and-in-vivo
#1
Wenbo Ren, Yang Li, Xiaojing Xia, Wenfei Guo, Taiyu Zhai, Yuting Jin, Yanyi Che, Haidi Gao, Xiumei Duan, Tinghao Huang, Jing Huang, Liancheng Lei
Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway...
May 7, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29733580/leucine-affects-%C3%AE-amylase-synthesis-through-pi3k-akt-mtor-signaling-pathways-in-pancreatic-acinar-cells-of-dairy-calves
#2
Long Guo, Ziqi Liang, Chen Zheng, Baolong Liu, Qingyan Yin, Yangchun Cao, J H Yao
Dietary nutrients utilization, particularly starch, is potentially limited by digestion in dairy cow small intestine because of shortage of α-amylase. Leucine acts as an effective signal molecular in the mTOR signaling pathway, which regulats a series of biological processes, especially protein synthesis. It has been reported that leucine could affect α-amylase synthesis and secretion in ruminant pancreas, but mechanisms have not been elaborated. In this study, pancreatic acinar (PA) cells were used as a model to determine the cellular signal of leucine influence on α-amylase synthesis...
May 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29682569/functions-and-signaling-pathways-of-amino-acids-in-intestinal-inflammation
#3
REVIEW
Fang He, Chenlu Wu, Pan Li, Nengzhang Li, Dong Zhang, Quoqiang Zhu, Wenkai Ren, Yuanyi Peng
Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestinal inflammation...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29680783/arabidopsis-ilithyia-protein-is-necessary-for-proper-chloroplast-biogenesis-and-root-development-independent-of-eif2%C3%AE-phosphorylation
#4
I Faus, R Niñoles, V Kesari, P Llabata, E Tam, S G Nebauer, J Santiago, M T Hauser, J Gadea
One of the main mechanisms blocking translation after stress situations is mediated by phosphorylation of the α-subunit of the eukaryotic initiation factor 2 (eIF2), performed in Arabidopsis by the protein kinase GCN2 which interacts and is activated by ILITHYIA(ILA). ILA is involved in plant immunity and its mutant lines present phenotypes not shared by the gcn2 mutants. The functional link between these two genes remains elusive in plants. In this study, we show that, although both ILA and GCN2 genes are necessary to mediate eIF2α phosphorylation upon treatments with the aromatic amino acid biosynthesis inhibitor glyphosate, their mutants develop distinct root and chloroplast phenotypes...
April 12, 2018: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29660505/gcn2-deficiency-ameliorates-doxorubicin-induced-cardiotoxicity-by-decreasing-cardiomyocyte-apoptosis-and-myocardial-oxidative-stress
#5
Yue Wang, Tong Lei, Juntao Yuan, Yongguang Wu, Xiyue Shen, Junling Gao, Wei Feng, Zhongbing Lu
The clinical use of doxorubicin for cancer therapy is limited by its cardiotoxicity, which involves cardiomyocyte apoptosis and oxidative stress. Previously, we showed that general control nonderepressible 2 (GCN2), an eukaryotic initiation factor 2α (eIF2α) kinase, impairs the ventricular adaptation to chronic pressure overload by affecting cardiomyocyte apoptosis. However, the impact of GCN2 on Dox-induced cardiotoxicity has not been investigated. In the present study, we treated wild type (WT) and Gcn2-/- mice with four intraperitoneal injections (5 mg/kg/week) to induce cardiomyopathy...
April 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29626156/the-gcn2-eif2a-pathway-connects-iron-and-amino-acid-homeostasis-in-saccharomyces-cerevisiae
#6
Marcos Caballero-Molada, María D Planes, Helena Benlloch, Sergio Atares, Miguel A Naranjo, Ramón Serrano
In eukaryotic cells amino acid biosynthesis is feedback inhibited by amino acids through inhibition of conserved protein kinase Gcn2. This decreases phosphorylation of initiation factor eIF2a resulting in general activation of translation but inhibition of translation of mRNA for transcription factor (TF) Gcn4 in yeast or ATF4 in mammals. These TFs are positive regulators of amino acid biosynthetic genes. As several enzymes of amino acid biosynthesis contain iron-sulfur clusters and iron excess is toxic, iron and amino acid homeostasis should be coordinated...
April 6, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29621237/amino-acid-starvation-sensing-dampens-il-1%C3%AE-production-by-activating-riboclustering-and-autophagy
#7
Srikanth Battu, Sumbul Afroz, Jeevan Giddaluru, Saima Naz, Weishan Huang, Saratchandra Singh Khumukcham, Rafiq Ahmad Khan, SaleemYousuf Bhat, Insaf Ahmed Qureshi, Bramanandam Manavathi, Aleem Ahmed Khan, Avery August, Seyed Ehtesham Hasnain, Nooruddin Khan
Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy...
April 5, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29609607/the-integrated-stress-response-regulates-bmp-signalling-through-effects-on-translation
#8
Elke Malzer, Caia S Dominicus, Joseph E Chambers, Jennifer A Dickens, Souradip Mookerjee, Stefan J Marciniak
BACKGROUND: Developmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress-sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Bone morphogenetic proteins (BMPs) regulate multiple developmental processes in organisms from insects to mammals. RESULTS: Here we show in Drosophila that GCN2 antagonises BMP signalling through direct effects on translation and indirectly via the transcription factor crc (dATF4)...
April 3, 2018: BMC Biology
https://www.readbyqxmd.com/read/29596413/lack-of-2-o-methylation-in-the-trna-anticodon-loop-of-two-phylogenetically-distant-yeast-species-activates-the-general-amino-acid-control-pathway
#9
Lu Han, Michael P Guy, Yoshiko Kon, Eric M Phizicky
Modification defects in the tRNA anticodon loop often impair yeast growth and cause human disease. In the budding yeast Saccharomyces cerevisiae and the phylogenetically distant fission yeast Schizosaccharomyces pombe, trm7Δ mutants grow poorly due to lack of 2'-O-methylation of C32 and G34 in the tRNAPhe anticodon loop, and lesions in the human TRM7 homolog FTSJ1 cause non-syndromic X-linked intellectual disability (NSXLID). However, it is unclear why trm7Δ mutants grow poorly. We show here that despite the fact that S...
March 29, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29570992/amino-acid-restriction-triggers-angiogenesis-via-gcn2-atf4-regulation-of-vegf-and-h-2-s-production
#10
Alban Longchamp, Teodelinda Mirabella, Alessandro Arduini, Michael R MacArthur, Abhirup Das, J Humberto Treviño-Villarreal, Christopher Hine, Issam Ben-Sahra, Nelson H Knudsen, Lear E Brace, Justin Reynolds, Pedro Mejia, Ming Tao, Gaurav Sharma, Rui Wang, Jean-Marc Corpataux, Jacques-Antoine Haefliger, Kyo Han Ahn, Chih-Hao Lee, Brendan D Manning, David A Sinclair, Christopher S Chen, C Keith Ozaki, James R Mitchell
Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α...
March 22, 2018: Cell
https://www.readbyqxmd.com/read/29531817/gcn2-controls-the-cellular-checkpoint-potential-target-for-regulating-inflammation
#11
EDITORIAL
Xiaojing Xia, Liancheng Lei, Wanhai Qin, Lei Wang, Gaiping Zhang, Jianhe Hu
No abstract text is available yet for this article.
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29499090/arabidopsis-nonresponding-to-oxylipins-locus-noxy7-encodes-a-yeast-gcn1-homolog-that-mediates-noncanonical-translation-regulation-and-stress-adaptation
#12
Yovanny Izquierdo, Satish Kulasekaran, Pablo Benito, Bran López, Ruth Marcos, Tomás Cascón, Mats Hamberg, Carmen Castresana
Stress adaptation and translational regulation was studied using noxy7 (nonresponding to oxylipins7) from a series of Arabidopsis thaliana mutants. We identified the noxy7 mutation in At1g64790, which encodes a homolog of the yeast translational regulator General Control Nonderepressible1 (GCN1) that activates the GCN2 kinase; GCN2 in turn phosphorylates the α subunit of the translation initiation factor eIF2. This regulatory circuit is conserved in yeast and mammals, in which phosphorylated eIF2α (P-eIF2α) facilitates stress adaptation by inhibiting protein synthesis...
March 2, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29449374/time-resolved-analysis-of-amino-acid-stress-identifies-eif2-phosphorylation-as-necessary-to-inhibit-mtorc1-activity-in-liver
#13
Inna A Nikonorova, Emily T Mirek, Christina C Signore, Michael P Goudie, Ronald C Wek, Tracy G Anthony
Amino acid availability is sensed by GCN2 (general control nonderepressible 2) and mechanistic target of rapamycin complex 1 (mTORC1), but how these two sensors coordinate their respective signal transduction events remains mysterious. In this study we utilized mouse genetic models to investigate the role of GCN2 in hepatic mTORC1 regulation upon amino acid stress induced by a single injection of asparaginase. We found that deletion of Gcn2 prevented hepatic phosphorylation of eukaryotic initiation factor 2α to asparaginase and instead unleashed mTORC1 activity...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29434187/glutamine-metabolism-regulates-flip-expression-and-sensitivity-to-trail-in-triple-negative-breast-cancer-cells
#14
Marta Mauro-Lizcano, Abelardo López-Rivas
Glutamine plays an important role in the metabolism of tumor cells through its contribution to redox homeostasis, bioenergetics, synthesis of macromolecules, and signaling. Triple-negative breast cancers (TNBC) are highly metastatic and associated with poor prognosis. TNBC cells show a marked dependence on extracellular glutamine for growth. Herein we demonstrate that TNBC cells are markedly sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis upon glutamine deprivation...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29432178/general-amino-acid-control-in-fission-yeast-is-regulated-by-a-nonconserved-transcription-factor-with-functions-analogous-to-gcn4-atf4
#15
Caia D S Duncan, María Rodríguez-López, Phil Ruis, Jürg Bähler, Juan Mata
Eukaryotes respond to amino acid starvation by enhancing the translation of mRNAs encoding b-ZIP family transcription factors ( GCN4 in Saccharomyces cerevisiae and ATF4 in mammals), which launch transcriptional programs to counter this stress. This pathway involves phosphorylation of the eIF2 translation factor by Gcn2-protein kinases and is regulated by upstream ORFs (uORFs) in the GCN4 / ATF4 5' leaders. Here, we present evidence that the transcription factors that mediate this response are not evolutionarily conserved...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29402369/-effect-of-silencing-aquaporin-4-on-learning-and-memory-dysfunction-in-rats-with-traumatic-brain-injury
#16
Ao Xiong, Ge Jin, Renping Xiong, Hong Lu
OBJECTIVE: To observe the protein expression related to cognitive and learning memory function, and to investigate the effect of aquaporin 4 (AQP4) silence on learning and memory function in traumatic brain injury (TBI) rats. METHODS: Ninety-six healthy adult male Wistar rats were divided into groups according to the random number table. (1) Forty-eight rats were divided into sham operation (sham) group, TBI group (by using modified Feeney method), AQP4 RNA interference (RNAi) negative group [TBI+meaningless small interfering RNA (siRNA)-AQP4 liposome solution 10 μL], and AQP4 RNAi group (TBI+siRNA-AQP4 liposome solution 10 μL)...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29383104/chac1-degradation-of-glutathione-enhances-cystine-starvation-induced-necroptosis-and-ferroptosis-in-human-triple-negative-breast-cancer-cells-via-the-gcn2-eif2%C3%AE-atf4-pathway
#17
Meng-Shian Chen, Sheng-Fan Wang, Chih-Yi Hsu, Pen-Hui Yin, Tien-Shun Yeh, Hsin-Chen Lee, Ling-Ming Tseng
Cancer cells exhibit an abnormal amino acid metabolism and a dependence on specific amino acids, which might provide potential targets for treating cancer patients. In this study, we demonstrated that human triple negative breast cancer (TNBC) cells were highly susceptible to cystine starvation. We found that necrostatin-1 (Nec-1, a RIP1 inhibitor), necrosulfonamide (an MLKL inhibitor), deferoxamine (an ion chelator), ferrostatin-1 (a ferroptosis inhibitor) and RIP1 knockdown can prevent cystine-starvation-induced cell death, suggesting that cystine starvation induces necroptosis and ferroptosis in TNBC cells...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29377765/autophagy-contributes-to-sulfonylurea-herbicide-tolerance-via-gcn2-independent-regulation-of-amino-acid-homeostasis
#18
Lun Zhao, Li Deng, Qing Zhang, Xue Jing, Meng Ma, Bin Yi, Jing Wen, Chaozhi Ma, Jinxing Tu, Tingdong Fu, Jinxiong Shen
Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved in SU tolerance. Here, we report a novel SU tolerance mechanism, autophagy, which we call 'homeostatic tolerance,' is involved in amino acid signaling in Arabidopsis. The activation and reversion of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for the activation of autophagy and GCN2...
January 29, 2018: Autophagy
https://www.readbyqxmd.com/read/29337352/genetic-removal-of-eif2%C3%AE-kinase-perk-in-mice-enables-hippocampal-l-ltp-independent-of-mtorc1-activity
#19
Helena R Zimmermann, Wenzhong Yang, Brenna C Beckelman, Nicole P Kasica, Xueyan Zhou, Lucas Galli, Alexey G Ryazanov, Tao Ma
Characterization of the molecular signaling pathways underlying protein synthesis-dependent forms of synaptic plasticity, such as late long-term potentiation (L-LTP), can provide insights not only into memory expression/maintenance under physiological conditions but also potential mechanisms associated with the pathogenesis of memory disorders. Here, we report in mice that L-LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2α (eIF2α)...
January 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29326164/the-glutamine-transporter-asct2-slc1a5-promotes-tumor-growth-independently-of-the-amino-acid-transporter-lat1-slc7a5
#20
Yann Cormerais, Pierre André Massard, Milica Vucetic, Sandy Giuliano, Eric Tambutté, Jerome Durivault, Valérie Vial, Hitoshi Endou, Michael F Wempe, Scott K Parks, Jacques Pouyssegur
The transporters for glutamine and essential amino acids, ASCT2 (solute carrier family 1 member 5, SLC1A5) and LAT1 (solute carrier family 7 member 5, SLC7A5), respectively, are overexpressed in aggressive cancers and have been identified as cancer-promoting targets. Moreover, previous work has suggested that glutamine influx via ASCT2 triggers essential amino acids entry via the LAT1 exchanger, thus activating mechanistic target of rapamycin complex 1 (mTORC1) and stimulating growth. Here, to further investigate whether these two transporters are functionally coupled, we compared the respective knockout (KO) of either LAT1 or ASCT2 in colon (LS174T) and lung (A549) adenocarcinoma cell lines...
February 23, 2018: Journal of Biological Chemistry
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