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mTOR AND Leucine

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https://www.readbyqxmd.com/read/28598238/nlrc3-regulates-cellular-proliferation-and-apoptosis-to-attenuate-the-development-of-colorectal-cancer
#1
Rajendra Karki, R K Subbarao Malireddi, Qifan Zhu, Thirumala-Devi Kanneganti
Nucleotide-binding domain, leucine-rich-repeat-containing proteins (NLRs) are intracellular innate immune sensors of pathogen-associated and damage-associated molecular patterns. NLRs regulate diverse biological processes such as inflammatory responses, cell proliferation and death, and gut microbiota to attenuate tumorigenesis. In a recent publication in Nature, we identified NLRC3 as a negative regulator of PI3K-mTOR signaling and characterized its potential tumor suppressor function. Enterocytes lacking NLRC3 cannot control cellular proliferation because they are unable to suppress activation of PI3K-mTOR signaling pathways...
June 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28583467/leucine-reduces-reactive-oxygen-species-levels-via-an-energy-metabolism-switch-by-activation-of-the-mtor-hif-1%C3%AE-pathway-in-porcine-intestinal-epithelial-cells
#2
Jun Hu, Yangfan Nie, Shifeng Chen, Chunlin Xie, Qiwen Fan, Zhichang Wang, Baisheng Long, Guokai Yan, Qing Zhong, Xianghua Yan
Leucine serves not only as a substrate for protein synthesis, but also as a signal molecule involved in protein metabolism. However, whether the levels of cellular reactive oxygen species (ROS), which have damaging effects on cellular DNA, proteins, and lipids, are regulated by leucine is still unclear. Here, we report that leucine supplementation reduces ROS levels in intestinal epithelial cells of weaned piglets. A proteomics analysis revealed that leucine supplementation induces an energy metabolism switch from oxidative phosphorylation (OXPHOS) towards glycolysis...
June 2, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28580286/role-of-nutrients-and-mtor-signaling-in-the-regulation-of-pancreatic-progenitors-development
#3
Lynda Elghazi, Manuel Blandino-Rosano, Emilyn Alejandro, Corentin Cras-Méneur, Ernesto Bernal-Mizrachi
OBJECTIVE: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28569781/mitochondrial-akap1-supports-mtor-pathway-and-tumor-growth
#4
Laura Rinaldi, Maria Sepe, Rossella Delle Donne, Kristel Conte, Antonietta Arcella, Domenica Borzacchiello, Stefano Amente, Fernanda De Vita, Monia Porpora, Corrado Garbi, Maria A Oliva, Claudio Procaccini, Deriggio Faicchia, Giuseppe Matarese, Federica Zito Marino, Gaetano Rocco, Sara Pignatiello, Renato Franco, Luigi Insabato, Barbara Majello, Antonio Feliciello
Mitochondria are the powerhouses of energy production and the sites where metabolic pathway and survival signals integrate and focus, promoting adaptive responses to hormone stimulation and nutrient availability. Increasing evidence suggests that mitochondrial bioenergetics, metabolism and signaling are linked to tumorigenesis. AKAP1 scaffolding protein integrates cAMP and src signaling on mitochondria, regulating organelle biogenesis, oxidative metabolism and cell survival. Here, we provide evidence that AKAP1 is a transcriptional target of Myc and supports the growth of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28566814/endocrine-responses-and-acute-mtor-pathway-phosphorylation-to-resistance-exercise-with-leucine-and-whey
#5
M T Lane, T J Herda, A C Fry, M A Cooper, M J Andre, P M Gallagher
Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises...
June 2017: Biology of Sport
https://www.readbyqxmd.com/read/28554316/beta-hydroxy-beta-methyl-butyrate-hmb-from-experimental-data-to-clinical-evidence-in-sarcopenia
#6
Alfonso J Cruz-Jentoft
β-hydroxy-β-methylbutyrate (HMB) is a metabolite derived from leucine and its ketoacid alpha-ketoisocaproate. Leucine has a role in regulating protein synthesis in muscle cells, and HMB seems to be a key active metabolite in such regulation. HMB has been shown to modulate muscle protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway, to up-regulate protein synthesis via the mTOR pathway, and to stabilize cell membranes via the rate limiting enzyme to cholesterol synthesis HMG- coenzyme A reductase...
May 28, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28554144/muscle-specific-deletion-of-socs3-does-not-reduce-the-anabolic-response-to-leucine-in-a-mouse-model-of-acute-inflammation
#7
M K Caldow, D J Ham, A Chee, J Trieu, T Naim, D I Stapleton, K Swiderski, G S Lynch, R Koopman
Excessive inflammation reduces skeletal muscle protein synthesis leading to wasting and weakness. The janus kinase/signal transducers and activators of transcription-3 (JAK/STAT3) pathway is important for the regulation of inflammatory signaling. As such, suppressor of cytokine signaling-3 (SOCS3), the negative regulator of JAK/STAT signaling, is thought to be important in the control of muscle homeostasis. We hypothesized that muscle-specific deletion of SOCS3 would impair the anabolic response to leucine during an inflammatory insult...
May 25, 2017: Cytokine
https://www.readbyqxmd.com/read/28536139/effects-of-leucine-supplementation-and-resistance-training-on-myopathy-of-diabetic-rats
#8
Carlos Eduardo C Martins, Vanessa B de S Lima, Brad J Schoenfeld, Julio Tirapegui
Leucine supplementation and resistance training positively influence the protein translation process and the cell signaling mTOR (mammalian target of rapamycin) pathway that regulates muscle protein balance and muscle remodeling, and thus may be therapeutic to diabetic myopathy. However, the effect of a combined intervention has not been well studied. Forty male Wistar rats were divided into five groups, control (C), diabetic control (D), diabetic + trained (DT), diabetic + L-leucine (DL), diabetic + L-leucine + trained (DLT)...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28413737/amino-acid-leucine-chromatography-a-study-of-branched-chain-aminoaciduria-in-type-2-diabetes
#9
Bhagavan Reddy Kolanu, Venugopal Boddula, Sabitha Vadakedath, Venkataramana Kandi
INTRODUCTION: Diabetes is a disease characterized by insulin deficiency resulting in glucose intolerance and in abnormalities of other metabolic fuels including protein. Recently, a number of studies have revealed that branched-chain amino acids (BCAAs) (leucine, isoleucine, and valine) play an important role in the regulation of protein synthesis by activating mammalian target of rapamycin (mTOR) in pancreatic β cells. BCAAs have positive effects on the regulation of glucose homeostasis...
March 12, 2017: Curēus
https://www.readbyqxmd.com/read/28409828/leucine-elicits-myotube-hypertrophy-and-enhances-maximal-contractile-force-in-tissue-engineered-skeletal-muscle-in-vitro
#10
N R W Martin, M C Turner, R Farrington, D J Player, M P Lewis
The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilised a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signalling, myotube growth and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20mM of leucine inducing similar effects, which were greater than those seen with 1mM...
April 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28341273/branched-chain-amino-acids-enhance-cyst-development-in-autosomal-dominant-polycystic-kidney-disease
#11
Junya Yamamoto, Saori Nishio, Fumihiko Hattanda, Daigo Nakazawa, Toru Kimura, Michio Sata, Minoru Makita, Yasunobu Ishikawa, Tatsuya Atsumi
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1(flox/flox):Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age...
March 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28341051/whey-protein-derived-exosomes-increase-protein-synthesis-and-hypertrophy-in-c2-c12-myotubes
#12
C Brooks Mobley, Petey W Mumford, John J McCarthy, Michael E Miller, Kaelin C Young, Jeffrey S Martin, Darren T Beck, Christopher M Lockwood, Michael D Roberts
We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments...
January 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28336113/effect-of-branched-chain-amino-acid-ratio-on-the-proliferation-differentiation-and-expression-levels-of-key-regulators-involved-in-protein-metabolism-of-myocytes
#13
Yehui Duan, Liming Zeng, Fengna Li, Wenlong Wang, Yinghui Li, Qiuping Guo, Yujiao Ji, Bi'e Tan, Yulong Yin
OBJECTIVES: Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are key regulators of protein synthesis in muscle. The aim of this study was to investigate the effect of different BCAA ratios (Leu:Ile:Val) on the proliferation, differentiation, and expression levels of the regulators related to protein metabolism of C2 C12 myocytes. METHODS: Studies were conducted in C2C12 myocytes exposed to different BCAA ratios (Leu: Ile: Val = 0, 1:0...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#14
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28242177/structure-activity-relationship-of-a-novel-series-of-inhibitors-for-cancer-type-transporter-l-type-amino-acid-transporter-1-lat1
#15
Pornparn Kongpracha, Shushi Nagamori, Pattama Wiriyasermkul, Yoko Tanaka, Kazuko Kaneda, Suguru Okuda, Ryuichi Ohgaki, Yoshikatsu Kanai
L-type amino acid transporter 1 (LAT1) is known as a cancer-type amino acid transporter. In cancer cells, LAT1 is responsible for the cellular uptake of many essential amino acids including leucine that activates mechanistic/mammalian target of rapamycin (mTOR), regulating cancer cell growth. In this study, we designed a novel series of LAT1 inhibitors, SKN101-105, based on the structure of triiodothyronine (T3), a known LAT1 blocker. The compounds consist of core structure of 2-amino-3-[3,5-dichloro-4-(naphthalene-1-methoxy)-phenyl]-propanoic acid and different modifications on the naphthalene...
February 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28237591/methionine-leucine-isoleucine-or-threonine-effects-on-mammary-cell-signaling-and-pup-growth-in-lactating-mice
#16
G M Liu, M D Hanigan, X Y Lin, K Zhao, F G Jiang, R R White, Y Wang, Z Y Hu, Z H Wang
Two studies were undertaken to assess the effects of individual essential AA supplementation of a protein-deficient diet on lactational performance in mice using litter growth rates as a response variable. The first study was designed to establish a dietary protein response curve, and the second to determine the effects of Leu, Ile, Met, and Thr supplementation of a protein-deficient diet on lactational performance. In both studies, dams were fed test diets from parturition through d 17 of lactation, when the studies ended...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28214587/paqr3-augments-amino-acid-deprivation-induced-autophagy-by-inhibiting-mtorc1-signaling
#17
Lin Wang, Yi Pan, Meiqin Huang, Xue You, Feifan Guo, Yan Chen
Amino acids are the key activators of the mTOR complex 1 (mTORC1, mainly composed of mTOR, Raptor and mLST8) required for cell growth and proliferation. On the other hand, deprivation of amino acids induces autophagy via inhibition of mTORC1 signaling. We report here that amino acid-induced mTORC1 activity and amino acid deprivation-induced autophagy are regulated by PAQR3, a newly found tumor suppressor. At the cellular level, PAQR3 negatively regulates amino acid-induced activation of mTORC1. The N-terminal end of PAQR3 interacts with the WD domains of Raptor and mLST8 directly...
February 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28127425/novel-metabolic-and-physiological-functions-of-branched-chain-amino-acids-a-review
#18
REVIEW
Shihai Zhang, Xiangfang Zeng, Man Ren, Xiangbing Mao, Shiyan Qiao
It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28115977/efficacy-of-a-novel-formulation-of-l-carnitine-creatine-and-leucine-on-lean-body-mass-and-functional-muscle-strength-in-healthy-older-adults-a-randomized-double-blind-placebo-controlled-study
#19
Malkanthi Evans, Najla Guthrie, John Pezzullo, Toran Sanli, Roger A Fielding, Aouatef Bellamine
BACKGROUND: Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects. METHOD: Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 μg) (L-Carnitine-combination) product (n = 14), L-Carnitine (1500 mg) (n = 14), or a placebo (n = 14) for eight weeks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#20
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
March 2017: Free Radical Biology & Medicine
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