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target of rapamycin

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https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#1
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28820083/threonine-deficiency-decreased-intestinal-immunity-and-aggravated-inflammation-associated-with-nf-%C3%AE%C2%BAb-and-target-of-rapamycin-signalling-pathways-in-juvenile-grass-carp-ctenopharyngodon-idella-after-infection-with-aeromonas-hydrophila
#2
Yu-Wen Dong, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99-21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling...
July 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28819418/cenph-inhibits-rapamycin-sensitivity-by-regulating-golph3-dependent-mtor-signaling-pathway-in-colorectal-cancer
#3
Wei Wu, Fan Wu, Zaozao Wang, Jiabo Di, Jie Yang, Pin Gao, Beihai Jiang, Xiangqian Su
Background: Centromere protein H (CENPH) is known as a fundamental component of the active centromere complex, and its overexpression is correlated with poor prognosis in various solid tumors. mTOR inhibitor rapamycin has been shown to possess antitumor activity, as well as prevent intestinal tumorigenesis. However, the prognostic value of CENPH in colorectal cancer (CRC) and the role of CENPH in rapamycin sensitivity remain unknown. Materials and methods: The effect of CENPH on the cell proliferation, clonogenicity, and cell response to rapamycin in CRC were evaluated by MTT and/or colony formation assays...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819378/hif-is-not-essential-for-suppression-of-experimental-tumor-growth-by-mtor-inhibition
#4
Karl X Knaup, Regina Guenther, Johanna Stoeckert, Juliana M Monti, Kai-Uwe Eckardt, Michael S Wiesener
The Hypoxia Inducible Transcription Factor (HIF) is the master regulator of cellular response to hypoxic adaptation. Solid tumors inevitably harbour hypoxic regions with subsequent stabilization and activation of HIF and HIF target genes due to poor vascularization and rapid growth. The mammalian target of rapamycin (mTOR) is a global regulator of cellular growth and proliferation, which can also regulate HIF expression independantly of hypoxia via specific activation of cellular translation and transcription...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818847/a-french-cohort-study-of-kidney-retransplantation-after-post-transplant-lymphoproliferative-disorders
#5
Sophie Caillard, Etienne Cellot, Jacques Dantal, Olivier Thaunat, François Provot, Bénédicte Janbon, Matthias Buchler, Dany Anglicheau, Pierre Merville, Philippe Lang, Luc Frimat, Charlotte Colosio, Eric Alamartine, Nassim Kamar, Anne Elisabeth Heng, Antoine Durrbach, Valérie Moal, Joseph Rivalan, Isabelle Etienne, Marie Noelle Peraldi, Anne Moreau, Bruno Moulin
BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorders arising after kidney transplantation portend an increased risk of morbidity and mortality. Retransplantation of patients who had developed post-transplant lymphoproliferative disorder remains questionable owing to the potential risks of recurrence when immunosuppression is reintroduced. Here, we investigated the feasibility of kidney retransplantation after the development of post-transplant lymphoproliferative disorder...
August 17, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28818096/immunohistochemical-prognostic-markers-of-esophageal-squamous-cell-carcinoma-a-systematic-review
#6
Chunni Wang, Jingnan Wang, Zhaoli Chen, Yibo Gao, Jie He
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC. METHODS: We conducted a systematic review on immunohistochemical (IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines...
August 17, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28817601/bortezomib-initiates-endoplasmic-reticulum-stress-elicits-autophagy-and-death-in-echinococcus-granulosus-larval-stage
#7
María Celeste Nicolao, Julia A Loos, Christian Rodriguez Rodrigues, Viviana Beas, Andrea C Cumino
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#8
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#9
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28816239/hippocampal-protein-kinase-c-signaling-mediates-the-short-term-memory-impairment-induced-by-delta9-tetrahydrocannabinol
#10
Arnau Busquets-Garcia, Maria Gomis-González, Victòria Salgado-Mendialdúa, Lorena Galera-López, Emma Puighermanal, Elena Martín-García, Rafael Maldonado, Andrés Ozaita
Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors, prevented the short-term, but not the long-term, memory impairment induced by THC...
August 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28815872/a-multimethod-computational-simulation-approach-for-investigating-mitochondrial-dynamics-and-dysfunction-in-degenerative-aging
#11
Timothy E Hoffman, Katherine J Barnett, Lyle Wallis, William H Hanneman
Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans...
August 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#12
Ryan T Sowell, Josef W Goldufsky, Magdalena Rogozinska, Zurisaday Quiles, Yanxia Cao, Eliseo F Castillo, Alison Finnegan, Amanda L Marzo
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#13
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813526/mtor-has-a-developmental-stage-specific-role-in-mitochondrial-fitness-independent-of-conventional-mtorc1-and-mtorc2-and-the-kinase-activity
#14
Khalid W Kalim, Shuangmin Zhang, Xiaoyi Chen, Yuan Li, Jun-Qi Yang, Yi Zheng, Fukun Guo
The mammalian target of rapamycin (mTOR), present in mTOR complex 1 (mTORC1) and mTORC2, is a serine/threonine kinase that integrates nutrients, growth factors, and cellular energy status to control protein synthesis, cell growth, survival and metabolism. However, it remains elusive whether mTOR plays a developmental stage-specific role in tissue development and whether mTOR can function independent of its complexes and kinase activity. In this study, by inducible genetic manipulation approach, we investigated the role of mTOR and its dependence on mTOR complexes and kinase activity in mitochondrial fitness of early, progenitor stage (lineage-negative; Lin-) versus later, lineage-committed stage (lineage-positive; Lin+) of hematopoietic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#15
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811537/prognostic-significance-and-function-of-mammalian-target-of-rapamycin-in-tongue-squamous-cell-carcinoma
#16
Shau-Hsuan Li, Chih-Yen Chien, Wan-Ting Huang, Sheng-Dean Luo, Yan-Ye Su, Wan-Yu Tien, Ya-Chun Lan, Chang-Han Chen
Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#17
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#18
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28810701/yeast-genes-involved-in-regulating-cysteine-uptake-affect-production-of-hydrogen-sulfide-from-cysteine-during-fermentation
#19
Chien-Wei Huang, Michelle E Walker, Bruno Fedrizzi, Richard C Gardner, Vladimir Jiranek
An early burst of hydrogen sulfide (H2S) produced by Saccharomyces cerevisiae during fermentation could increase varietal thiols and therefore enhance desirable tropical aromas in varieties such as Sauvignon Blanc. Here we attempted to identify genes affecting H2S formation from cysteine by screening yeast deletion libraries via a colony colour assay on media resembling grape juice. Both Δlst4 and Δlst7 formed lighter coloured colonies and produced significantly less H2S than the wild type on high concentrations of cysteine, likely because they are unable to take up cysteine efficiently...
August 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28810557/role-of-mammalian-target-of-rapamycin-signaling-in-autophagy-and-the-neurodegenerative-process-using-a-senescence-accelerated-mouse-prone-8-model
#20
Yanyong Wang, Qinying Ma, Xiaowei Ma, Zhongxia Zhang, Na Liu, Mingwei Wang
The mammalian target of rapamycin (mTOR) kinase is an inhibitor of autophagy, which is an intracellular system involved in the degradation of long-lived proteins and organelles in lysosomes. Recent evidence suggests that the steady incline in mTOR function during aging may be associated with the cognitive decline related to aging and may also promote development of Tau pathology. At present, the senescence accelerated mouse prone 8 (SAMP8) is an experimental model that has been proposed for the study of age-related neurodegenerative changes associated with aging...
August 2017: Experimental and Therapeutic Medicine
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