keyword
MENU ▼
Read by QxMD icon Read
search

Mtorc1

keyword
https://www.readbyqxmd.com/read/28526373/coffee-consumption-in-aged-mice-increases-energy-production-and-decreases-hepatic-mtor-levels
#1
Keita Takahashi, Shuichi Yanai, Kentaro Shimokado, Akihito Ishigami
OBJECTIVE: Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. METHODS: Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28525387/sestrin-2-suppresses-cells-proliferation-through-ampk-mtorc1-pathway-activation-in-colorectal-cancer
#2
Jin-Lai Wei, Min Fang, Zhong-Xue Fu, Shou-Ru Zhang, Jin-Bao Guo, Rong Wang, Zhen-Bing Lv, Yong-Fu Xiong
Sestrin 2 is a conserved antioxidant protein that reduces reactive oxygen species (ROS) and inhibits mammalian target of rapamycin complex 1 (mTORC1). We previously showed that sestrin 2 is abnormally decreased in colorectal cancer (CRC). To elucidate the molecular mechanism behind the potential contribution of sestrin 2 to CRC, we used a lentiviral expression vector system to determine the effects of sestrin 2 overexpression on human CRC cells. We found that sestrin 2 overexpression decreased ROS production, inhibited cell growth, and stimulated apoptosis in two CRC cell lines...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523278/chondrocyte-specific-knockout-of-tsc-1-leads-to-congenital-spinal-deformity-in-mice
#3
Cheng Yang, Yuhui Chen, Zhen Li, He Cao, Keming Chen, Pinglin Lai, Bo Yan, Bin Huang, Jiajun Tang, Shicai Fan, Daozhang Cai, Dadi Jin, Xiaochun Bai, Rongping Zhou
Congenital spinal deformity is the most severe clinical orthopedic issue worldwide. Among all the pathological processes of congenital spinal deformity, the imbalance of endochondral ossification is considered to be the most important developmental cause of spinal dysplasia. We established chondrocyte-specific TSC-1 knockout (KO) mice to overactivate the energy metabolic component, mammalian target of rapamycin complex 1 (mTORC1), and measured the spinal development by general, imaging, histological, and Western-blot assessments...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28520214/mtorc1-inhibits-nf-%C3%AE%C2%BAb-nfatc1-signaling-and-prevents-osteoclast-precursor-differentiation-in-vitro-and-in-mice
#4
Yue Zhang, Song Xu, Kai Li, Kang Tan, Kangyan Liang, Jian Wang, Junhui Shen, Wenchong Zou, Le Hu, Daozhang Cai, Changhai Ding, Mangmang Li, Guozhi Xiao, Bin Liu, Anling Liu, Xiaochun Bai
The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast development and the underlying mechanisms have not yet been fully established. Here, we found that mTORC1 activity declined during osteoclast precursors differentiation in vitro and in vivo. We further targeted deletion of Raptor (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages), using LyzM-cre mice...
May 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28516268/gpna-inhibits-the-sodium-independent-transport-system-l-for-neutral-amino-acids
#5
Martina Chiu, Cosimo Sabino, Giuseppe Taurino, Massimiliano G Bianchi, Roberta Andreoli, Nicola Giuliani, Ovidio Bussolati
L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine...
May 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28512249/p62-sqstm1-cooperates-with-hyperactive-mtorc1-to-regulate-glutathione-production-maintain-mitochondrial-integrity-and-promote-tumorigenesis
#6
Hilaire C Lam, Christian V Baglini, Alicia Llorente Lope, Andrey Parkhitko, Heng-Jia Liu, Nicola Alesi, Izabela A Malinowska, Darius Ebrahimi-Fakhari, Afshin Saffari, Jane J Yu, Ana Pereira, Damir Khabibullin, Barbara Ogorek, Julie S Nijmeh, Taylor Kavanagh, Adam Handen, Stephen Y Chan, John M Asara, William M Oldham, Maria Diaz-Meco, Jorge Moscat, Mustafa Sahin, Carmen Priolo, Elizabeth P Henske
p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate which accumulates in cells with hyperactive mTORC1, such as kidney cells with mutations in the tumor suppressor genes TSC1 or TSC2. Here we report that p62 is a critical mediator of TSC2-driven tumorigenesis, as Tsc2+/- and Tsc2f/f Ksp-CreERT2+ mice crossed to p62-/- mice were protected from renal tumor development. Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH)...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28512198/novel-role-of-rac-mid1-signaling-in-medial-cerebellar-development
#7
Takashi Nakamura, Takehiko Ueyama, Yuzuru Ninoyu, Hirofumi Sakaguchi, Narantsog Choijookhuu, Yoshitaka Hishikawa, Hiroshi Kiyonari, Masaaki Kohta, Mizuho Sakahara, Ivan de Curtis, Eiji Kohmura, Yasuo Hisa, Atsu Aiba, Naoaki Saito
Rac signaling impacts a relatively large number of downstream targets; however, few studies have established an association between Rac pathways and pathological conditions. In the present study, we generated mice with double knockout of Rac1 and Rac3 (Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) ) in cerebellar granule neurons (CGNs). We observed impaired tangential migration at E16.5, as well as numerous apoptotic CGNs at the deepest layer of the external granule layer (EGL) in the medial cerebellum of Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) mice at P8...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#8
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507054/glutamine-transporters-are-targets-of-multiple-oncogenic-signaling-pathways-in-prostate-cancer
#9
Mark A White, Chenchu Lin, Kimal Rajapakshe, Jianrong Dong, Yan Shi, Efrosini Tsouko, Ratna Mukhopadhyay, Diana Jasso, Wajahat Dawood, Cristian Coarfa, Daniel E Frigo
Despite the known importance of androgen receptor (AR) signaling in prostate cancer (PCa), the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in PCa cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in PCa...
May 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28507025/cutting-edge-defective-aerobic-glycolysis-defines-the-distinct-effector-function-in-antigen-activated-cd8-recent-thymic-emigrants
#10
Cody A Cunningham, Tessa Bergsbaken, Pamela J Fink
Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have completed thymic selection and egress to the lymphoid periphery. RTEs are functionally distinct from their more mature but still naive T cell counterparts, because they exhibit dampened proliferation and reduced cytokine production upon activation. In this article, we show that, compared with more mature but still naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis following activation. Impaired metabolism underlies the reduced IFN-γ production observed in activated RTEs...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28505179/food-restriction-increase-the-expression-of-mtorc1-complex-genes-in-the-skeletal-muscle-of-juvenile-pacu-piaractus-mesopotamicus
#11
Tassiana Gutierrez de Paula, Bruna Tereza Thomazini Zanella, Bruno Evaristo de Almeida Fantinatti, Leonardo Nazário de Moraes, Bruno Oliveira da Silva Duran, Caroline Bredariol de Oliveira, Rondinelle Artur Simões Salomão, Rafaela Nunes da Silva, Carlos Roberto Padovani, Vander Bruno Dos Santos, Edson Assunção Mareco, Robson Francisco Carvalho, Maeli Dal-Pai-Silva
Skeletal muscle is capable of phenotypic adaptation to environmental factors, such as nutrient availability, by altering the balance between muscle catabolism and anabolism that in turn coordinates muscle growth. Small noncoding RNAs, known as microRNAs (miRNAs), repress the expression of target mRNAs, and many studies have demonstrated that miRNAs regulate the mRNAs of catabolic and anabolic genes. We evaluated muscle morphology, gene expression of components involved in catabolism, anabolism and energetic metabolism and miRNAs expression in both the fast and slow muscle of juvenile pacu (Piaractus mesopotamicus) during food restriction and refeeding...
2017: PloS One
https://www.readbyqxmd.com/read/28504970/osteoclast-proton-pump-regulator-atp6v1c1-enhances-breast-cancer-growth-by-activating-the-mtorc1-pathway-and-bone-metastasis-by-increasing-v-atpase-activity
#12
Matthew McConnell, Shengmei Feng, Wei Chen, Guochun Zhu, Dejun Shen, Selvarangan Ponnazhagan, Lianfu Deng, Yi-Ping Li
It is known that V-ATPases (vacuolar H+-ATPase) are involved in breast cancer growth and metastasis. Part of this action is similar to their role in osteoclasts, where they're involved in extracellular acidification and matrix destruction; however, the roles of their subunits in cancer cell proliferation, signaling, and other pro-tumor actions are not well established. Analysis of TCGA data shows that V-ATPase subunit Atp6v1c1 is overexpressed or amplified in 34% of human breast cancer cases, with a 2-fold decrease in survival at 12 years...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504707/regulation-of-mitochondrial-biogenesis-in-erythropoiesis-by-mtorc1-mediated-protein%C3%A2-translation
#13
Xin Liu, Yuannyu Zhang, Min Ni, Hui Cao, Robert A J Signer, Dan Li, Mushan Li, Zhimin Gu, Zeping Hu, Kathryn E Dickerson, Samuel E Weinberg, Navdeep S Chandel, Ralph J DeBerardinis, Feng Zhou, Zhen Shao, Jian Xu
Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28503190/essential-amino-acid-ingestion-alters-expression-of-genes-associated-with-amino-acid-sensing-transport-and-mtorc1-regulation-in-human-skeletal-muscle
#14
Ted G Graber, Michael S Borack, Paul T Reidy, Elena Volpi, Blake B Rasmussen
BACKGROUND: Amino acid availability stimulates protein synthesis via the mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. In response to an increase in cellular amino acid availability, translocation of cytosolic mTORC1 to the lysosomal surface is required to stimulate mTORC1 kinase activity. However, research elucidating the amino acid responsive mechanisms have thus far only been conducted in in vitro models. Our primary objective was to determine whether an increase in amino acid availability within human skeletal muscle in vivo would alter the expression of genes associated with amino acid sensing, transport and mTORC1 regulation...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28502587/direct-and-indirect-activation-of-eukaryotic-elongation-factor-2-kinase-by-amp-activated-protein-kinase
#15
M Johanns, S Pyr Dit Ruys, A Houddane, D Vertommen, G Herinckx, L Hue, C G Proud, M H Rider
BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions...
May 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28500078/a-time-and-compartment-specific-activation-of-lung-macrophages-in-hypoxic-pulmonary-hypertension
#16
Steven C Pugliese, Sushil Kumar, William J Janssen, Brian B Graham, Maria G Frid, Suzette R Riddle, Karim C El Kasmi, Kurt R Stenmark
Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28499951/effects-of-task-specific-rehabilitation-training-on-tau-modification-in-rat-with-photothrombotic-cortical-ischemic-damage
#17
Kyung-Lim Joa, Sohee Moon, Ji-Hye Kim, Dong Wun Shin, Kyoung-Hee Lee, Seon Jung, Myeong-Ok Kim, Chang-Hwan Kim, Han-Young Jung, Ju-Hee Kang
Although stroke elicits progressive cognitive decline and is a leading cause of dementia, molecular interplay between stroke and Alzheimer's disease (AD) pathology has not been fully elucidated. Furthermore, studies on the effects of post-stroke rehabilitation on AD pathology are limited. We evaluated the acute effect of stroke on tau modification, and the molecular effects of task-specific training (TST) on tau modification using a model of photochemically-induced thrombosis (PIT)-induced cortical infarction...
May 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28498820/lysosomal-regulation-of-cholesterol-homeostasis-in-tuberous-sclerosis-complex-is-mediated-via-npc1-and-ldl-r
#18
Harilaos Filippakis, Nicola Alesi, Barbara Ogorek, Julie Nijmeh, Damir Khabibullin, Catherine Gutierrez, Alexander J Valvezan, James Cunningham, Carmen Priolo, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#19
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28496395/a-relative-quantitative-positive-negative-ion-switching-method-for-untargeted-lipidomics-via-high-resolution-lc-ms-ms-from-any-biological-source
#20
Susanne B Breitkopf, Stéphane J H Ricoult, Min Yuan, Ying Xu, David A Peake, Brendan D Manning, John M Asara
INTRODUCTION: Advances in high-resolution mass spectrometry have created renewed interest for studying global lipid biochemistry in disease and biological systems. OBJECTIVES: Here, we present an untargeted 30 min. LC-MS/MS platform that utilizes positive/negative polarity switching to perform unbiased data dependent acquisitions (DDA) via higher energy collisional dissociation (HCD) fragmentation to profile more than 1000-1500 lipid ions mainly from methyl-tert-butyl ether (MTBE) or chloroform:methanol extractions...
March 2017: Metabolomics: Official Journal of the Metabolomic Society
keyword
keyword
38729
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"