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https://www.readbyqxmd.com/read/29914932/mtor-signaling-in-the-arcuate-nucleus-of-the-hypothalamus-mediates-the-anorectic-action-of-estradiol
#1
Ismael González-García, Pablo Blanco, Ánxela Estévez-Salguero, Cristina Contreras, Amparo Romero-Picó, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, Manuel Tena-Sempere, Sulay Tovar, Miguel López
Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that, ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism...
June 18, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29862445/expression-of-mirnas-targeting-mtor-and-s6k1-genes-of-mtor-signaling-pathway-including-mir-96-mir-557-and-mir-3182-in-triple-negative-breast-cancer
#2
Javad Razaviyan, Razie Hadavi, Rezvan Tavakoli, Fereshteh Kamani, Maliheh Paknejad, Samira Mohammadi-Yeganeh
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Aberrant expression of genes in mTOR pathway and their targeting miRNAs plays an important role in TNBC. The aim of this study was to determine the expression of mTOR and S6K1 and their targeting miRNAs in breast cancer cell lines and clinical samples. miRNAs targeting 3'-UTR of mTOR and S6K1 mRNAs were predicted using bioinformatic algorithms. MDA-MB-231, MCF-7, and MCF-10A as well as 20 TNBC samples were analyzed for gene and miRNA expression using quantitative real-time PCR (RT-qPCR)...
June 4, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29761287/activation-of-the-mtorc1-pathway-by-inflammation-contributes-to-vascular-calcification-in-patients-with-end-stage-renal-disease
#3
Jing Liu, Wei Zhu, Chun Ming Jiang, Yuan Feng, Yang Yang Xia, Qing Yan Zhang, Miao Zhang
BACKGROUND: Chronic inflammation plays an important role in the progression of vascular calcification (VC). This study was designed to explore the effects and underlying mechanisms of inflammation on VC in the radial arteries of patients with end-stage renal disease (ESRD) with arteriovenostomy. METHODS: Forty-eight ESRD patients were divided into control (n = 25) and inflammation groups (n = 23) according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in this study...
May 14, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29750193/mammalian-eak-7-activates-alternative-mtor-signaling-to-regulate-cell-proliferation-and-migration
#4
Joe Truong Nguyen, Connor Ray, Alexandra Lucienne Fox, Daniela Baccelli Mendonça, Jin Koo Kim, Paul H Krebsbach
Nematode EAK-7 (enhancer-of- akt -1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29743930/lxr%C3%A9-participates-in-the-mtor-s6k1-srebp-1c-signaling-pathway-during-sodium-palmitate-induced-lipogenesis-in-hepg2-cells
#5
Youping Zhou, Shengjie Yu, Can Cai, Li Zhong, Huihong Yu, Wei Shen
Background: The aim of this study was to investigate how the signaling pathway downstream of mTOR/S6K1 contributes to the regulation of SREBP-1c expression during lipogenesis in HepG2 cells. Methods: The model of steatosis was established using human hepatocytes HepG2 and inducting them with sodium palmitate. mTOR, S6K1 and LXRα were inhibited by rapamycin, PF-4708671 and siRNA-LXRα, respectively. After a variety of different treatment, the levels of intracellular triglycerides, the accumulation of lipid droplets and the expression levels of related genes were detected...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#6
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29734044/tombusvirus-rna-replication-depends-on-the-tor-pathway-in-yeast-and-plants
#7
Jun-Ichi Inaba, Peter D Nagy
Similar to other (+)RNA viruses, tomato bushy stunt virus (TBSV) utilizes metabolites, lipids, membranes, and co-opted host factors during replication. The coordination of cell metabolism and growth with environmental cues is performed by the target of rapamycin (TOR) kinase in eukaryotic cells. In this paper, we find that TBSV replication partially inhibits TOR activity, likely due to recruitment of glycolytic enzymes to the viral replication compartment, which results in reduced ATP levels in the cytosol...
May 4, 2018: Virology
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
#8
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/29729916/short-communication-high-incubation-temperature-in-bovine-mammary-epithelial-cells-reduced-the-activity-of-the-mtor-signaling-pathway
#9
J D Kaufman, K R Kassube, R A Almeida, A G Ríus
Hyperthermia alters utilization of AA in protein synthesis and cell-signaling activity in bovine mammary cells. Essential AA and insulin regulate translation of proteins by controlling the activity of mammalian target of rapamycin (mTOR) signaling pathway. The objectives of this study were to evaluate (1) the effects of incubation temperature on the mTOR signaling pathway and transcription of AA transporters in a bovine mammary alveolar cell line (MAC-T) and (2) the combined effects of incubation temperature and insulin on the mTOR signaling pathway in this cell line...
May 2, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29728917/short-and-long-term-effects-of-leucine-and-branched-chain-amino-acid-supplementation-of-a-protein-and-energy-reduced-diet-on-muscle-protein-metabolism-in-neonatal-pigs
#10
Rodrigo Manjarín, Daniel A Columbus, Jessica Solis, Adriana D Hernandez-García, Agus Suryawan, Hanh V Nguyen, Molly M McGuckin, Rafael T Jimenez, Marta L Fiorotto, Teresa A Davis
The objective of this study was to determine if enteral leucine or branched-chain amino acid (BCAA) supplementation increases muscle protein synthesis in neonates who consume less than their protein and energy requirements, and whether this increase is mediated via the upregulation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway or the decrease in muscle protein degradation signaling. Neonatal pigs were fed milk replacement diets containing reduced energy and protein (R), R supplemented with BCAA (RBCAA), R supplemented with leucine (RL), or complete protein and energy (CON) at 4-h intervals for 9 (n = 24) or 21 days (n = 22)...
May 4, 2018: Amino Acids
https://www.readbyqxmd.com/read/29700204/sunrise-measuring-translation-elongation-at-single-cell-resolution-by-means-of-flow-cytometry
#11
Rafael J Argüello, Marisa Reverendo, Andreia Mendes, Voahirana Camosseto, Adrian G Torres, Lluis Ribas de Pouplana, Serge A van de Pavert, Evelina Gatti, Philippe Pierre
The rate at which ribosomes translate mRNAs regulates protein expression by controlling co-translational protein folding and mRNA stability. Many factors regulate translation elongation, including tRNA levels, codon usage and phosphorylation of eukaryotic elongation factor 2 (eEF2). Current methods to measure translation elongation lack single-cell resolution, require expression of multiple transgenes and have never been successfully applied ex vivo Here, we show, by using a combination of puromycilation detection and flow cytometry (a method we call 'SunRiSE'), that translation elongation can be measured accurately in primary cells in pure or heterogenous populations isolated from blood or tissues...
May 31, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29699927/mtorc1-dependent-increase-in-oxidative-metabolism-in-pomc-neurons-regulates-food-intake-and-action-of-leptin
#12
Magalie Haissaguerre, Amandine Ferrière, Vincent Simon, Nicolas Saucisse, Nathalie Dupuy, Caroline André, Samantha Clark, Omar Guzman-Quevedo, Antoine Tabarin, Daniela Cota
OBJECTIVE: Nutrient availability modulates reactive oxygen species (ROS) production in the hypothalamus. In turn, ROS regulate hypothalamic neuronal activity and feeding behavior. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an important cellular integrator of the action of nutrients and hormones. Here we tested the hypothesis that modulation of mTORC1 activity, particularly in Proopiomelanocortin (POMC)-expressing neurons, mediates the cellular and behavioral effects of ROS...
June 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29699848/phosphorylation-of-wat1-human-lst8-homolog-is-critical-for-the-regulation-of-torc2-gad8-dependent-pathway-in-fission-yeast-schizosacchromyces-pombe
#13
Nafees Ahamad, Tanuj Sharma, Saman Khan, Mohammad Imran Siddiqi, Shakil Ahmed
Mammalian Lst8 interacts with the kinase domain of mTOR and stabilizes its interaction with Raptor regulating cell growth through the mTOR-S6K1 signalling pathway. Fission yeast Wat1, an ortholog of mammalian Lst8 is also an essential component of TOR complex 1 (TORC1) and TOR Complex 2 (TORC2) that control protein kinases essential for metabolic pathways. Here, we show that in response to osmotic stress, the Wat1 protein undergoes hyper-phosphorylation at S116 position. Wat1 interacts with the C-terminal region of Tor1 that also contain kinase domain...
May 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29673648/s6-kinase-1-plays-a-key-role-in-mitochondrial-morphology-and-cellular-energy-flow
#14
Quangdon Tran, Jae-Hun Jung, Jisoo Park, Hyunji Lee, Youngeun Hong, Hyeonjeong Cho, Minhee Kim, Sungjin Park, So-Hee Kwon, Seon-Hwan Kim, George Thomas, Kwang Pyo Kim, Myung-Haing Cho, Jongsun Park
Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1-KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondrial fraction...
August 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29665055/s6k1-controls-epigenetic-plasticity-for-the-expression-of-pancreatic-%C3%AE-%C3%AE-cell-marker-genes
#15
Sang Ah Yi, Jieun Lee, Jong Woo Park, Jihoon Han, Min Gyu Lee, Ki Hong Nam, Jee Hun Park, Hwamok Oh, Sung Jin Ahn, Saetbyul Kim, So Hee Kwon, Dong-Gyu Jo, Jeung-Whan Han
The failure of insulin production by pancreatic β cells is a common hallmark of type 1 diabetes mellitus (T1DM). Because administration of exogenous insulin is associated with diabetes-derived complications, endogenous α to β cell transition can be an attractive alternative. Although decreased β cell size and hypoinsulinaemia have been observed in S6K1-deficient mice, the molecular mechanism underlying the involvement of S6K1 in the transcriptional regulation of insulin remains elusive. Here, we show that the hypoinsulinaemic phenotype of S6K1-deficient mice stems from the dysregulated transcription of a set of genes required for insulin and glucagon production...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29628303/overexpression-of-tfeb-drives-a-pleiotropic-neurotrophic-effect-and-prevents-parkinson-s-disease-related-neurodegeneration
#16
Albert Torra, Annabelle Parent, Thais Cuadros, Beatriz Rodríguez-Galván, Esther Ruiz-Bronchal, Andrea Ballabio, Analía Bortolozzi, Miquel Vila, Jordi Bové
The possible implication of transcription factor EB (TFEB) as a therapeutic target in Parkinson's disease has gained momentum since it was discovered that TFEB controls lysosomal biogenesis and autophagy and that its activation might counteract lysosomal impairment and protein aggregation. However, the majority of putative direct targets of TFEB described to date is linked to a range of biological processes that are not related to the lysosomal-autophagic system. Here, we assessed the effect of overexpressing TFEB with an adeno-associated viral vector in mouse substantia nigra dopaminergic neurons...
February 27, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29621478/hyperglycemia-induced-bcl-2-bax-mediated-apoptosis-of-schwann-cells-via-mtorc1-s6k1-inhibition-in-diabetic-peripheral-neuropathy
#17
Lin Zhu, Jun Hao, Meijuan Cheng, Cuihong Zhang, Chunxiu Huo, Yaping Liu, Wei Du, Xianghong Zhang
Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques...
June 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29617677/the-mtor-kinase-inhibitor-cz415-inhibits-human-papillary-thyroid-carcinoma-cell-growth
#18
Xiaobin Li, Zongze Li, Yimin Song, Wenjing Liu, Ziwen Liu
BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) plays an important role in papillary thyroid carcinoma (PTC) cell progression. CZ415 is a novel, highly-efficient and specific mTOR kinase inhibitor. The current study tested the potential anti-tumor activity of CZ415 in human PTC cells. METHODS: The established (TPC-1 cell line) and primary human PTC cells were treated with CZ415. Cell survival and growth were tested by Cell Counting Kit-8 assay and BrdU ELISA assay, respectively...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29605662/the-mtor-cell-signaling-pathway-is-crucial-to-the-long-term-protective-effects-of-ischemic-postconditioning-against-stroke
#19
Peng Wang, Rong Xie, Michelle Cheng, Robert Sapolsky, Xunming Ji, Heng Zhao
Ischemic postconditioning (IPostC) protects against stroke, but few have studied the pathophysiological mechanisms of its long-term protective effects. Here, we investigated whether the mTOR pathway is involved in the long-term protective effects of IPostC. Stroke was induced in rats by distal middle cerebral artery occlusion (dMCAo) combined with 30 min of bilateral common carotid artery (CCA) occlusion, and IPostC was induced after the CCA release. Injury size and behavioral tests were measured up to 3 weeks post stroke...
May 29, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29588411/the-p85-isoform-of-the-kinase-s6k1-functions-as-a-secreted-oncoprotein-to-facilitate-cell-migration-and-tumor-growth
#20
Jianjun Zhang, Jianping Guo, Xing Qin, Bin Wang, Linli Zhang, Yingnan Wang, Wenjian Gan, Pier Paolo Pandolfi, Wantao Chen, Wenyi Wei
Cancer cells can remodel surrounding microenvironments to facilitate cell growth, invasion, and migration by secreting proteins that educate surrounding stromal cells. We report that p85S6K1 , the longest isoform of S6K (ribosomal protein S6 kinase), but not the shorter isoform p70S6K1 or p56S6K2 , was secreted from cancer cells through its HIV TAT-like, N-terminal six-arginine motif. The exogenously produced p85S6K1 protein entered cultured transformed and nontransformed cells to promote or confer malignant behaviors, leading to increased cell growth and migration...
March 27, 2018: Science Signaling
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