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leucine mtor

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https://www.readbyqxmd.com/read/29764979/the-complex-relationship-between-tfeb-transcription-factor-phosphorylation-and-subcellular-localization
#1
REVIEW
Rosa Puertollano, Shawn M Ferguson, James Brugarolas, Andrea Ballabio
The MiT-TFE family of basic helix-loop-helix leucine-zipper transcription factors includes four members: TFEB, TFE3, TFEC, and MITF Originally described as oncogenes, these factors play a major role as regulators of lysosome biogenesis, cellular energy homeostasis, and autophagy. An important mechanism by which these transcription factors are regulated involves their shuttling between the surface of lysosomes, the cytoplasm, and the nucleus. Such dynamic changes in subcellular localization occur in response to nutrient fluctuations and various forms of cell stress and are mediated by changes in the phosphorylation of multiple conserved amino acids...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29752834/h-2-o-2-induces-pp2a-demethylation-to-downregulate-mtorc1-signaling-in-hek293-cells
#2
Shen Tang, Fu Qin, Xinhang Wang, Ziwei Liang, Haiqing Cai, Laiming Mo, Yue Huang, Boyin Liang, Xuejing Wei, Qingqing Ao, Yilu Xu, Yuyang Liu, Deqiang Xiao, Songchao Guo, Cailing Lu, Xiyi Li
Mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to govern cell growth and proliferation by mediating mitogen- and nutrient-dependent signal transduction. Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, negatively regulates mTOR signaling. Methylation of PP2A is catalyzed by leucine carboxyl methyltransferase-1 (LCMT1) and reversed by protein phosphatase methylesterase 1 (PME-1), which regulates PP2A activity and substrate specificity...
May 12, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29742868/modulated-gene-expression-of-toxoplasma-gondii-infected-retinal-pigment-epithelial-cell-line-arpe-19-via-pi3k-akt-or-mtor-signal-pathway
#3
Wei Zhou, Juan-Hua Quan, Fei-Fei Gao, Hassan Ahmed Hassan Ahmed Ismail, Young-Ha Lee, Guang-Ho Cha
Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes...
April 2018: Korean Journal of Parasitology
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
#4
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/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
#5
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/29723221/impact-of-silencing-hepatic-srebp-1-on-insulin-signaling
#6
Victoria Jideonwo, Yongyong Hou, Miwon Ahn, Sneha Surendran, Núria Morral
Sterol Regulatory Element Binding Protein-1 (SREBP-1) is a conserved transcription factor of the basic helix-loop-helix leucine zipper family (bHLH-Zip) that plays a central role in regulating expression of genes of carbohydrate and fatty acid metabolism in the liver. SREBP-1 activity is essential for the control of insulin-induced anabolic processes during the fed state. In addition, SREBP-1 regulates expression of key molecules in the insulin signaling pathway, including insulin receptor substrate 2 (IRS2) and a subunit of the phosphatidylinositol 3-kinase (PI3K) complex, PIK3R3, suggesting that feedback mechanisms exist between SREBP-1 and this pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29721955/how-excessive-cgmp-impacts-metabolic-proteins-in-retinas-at-the-onset-of-degeneration
#7
Jianhai Du, Jie An, Jonathan D Linton, Yekai Wang, James B Hurley
Aryl-hydrocarbon receptor interacting protein-like 1 (AIPL1) is essential to stabilize cGMP phosphodiesterase 6 (PDE6) in rod photoreceptors. Mutation of AIPL1 leads to loss of PDE6, accumulation of intracellular cGMP, and rapid degeneration of rods. To understand the metabolic basis for the photoreceptor degeneration caused by excessive cGMP, we performed proteomics and phosphoproteomics analyses on retinas from AIPL1-/- mice at the onset of rod cell death. AIPL1-/- retinas have about 18 times less than normal PDE6a and no detectable PDE6b...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29584425/leucine-promotes-the-growth-of-fetal-pigs-by-increasing-protein-synthesis-through-the-mtor-signaling-pathway-in-longissimus-dorsi-muscle-at-late-gestation
#8
Chaoxian Wang, Fang Chen, Wenfei Zhang, Shihai Zhang, Kui Shi, Hanqing Song, Yijiang Wang, Sun Woo Kim, Wutai Guan
Leucine (Leu) plays an important role in protein synthesis and metabolism. The present study tested whether Leu supplementation in the diet for sows during late pregnancy could improve piglet birth weight, and also investigated the possible underlying mechanism. Two hundreds sows at day 70 of pregnancy were selected and assigned to four groups fed with following four diets until farrowing respectively: corn and soybean meal-based diet group (CON), CON + 0.40% Leu, CON + 0.80% Leu and CON + 1.20% Leu. We found that supplementing with 0...
March 27, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29570613/branched-chain-amino-acids-beyond-nutrition-metabolism
#9
REVIEW
Cunxi Nie, Ting He, Wenju Zhang, Guolong Zhang, Xi Ma
Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in the regulation of energy homeostasis, nutrition metabolism, gut health, immunity and disease in humans and animals. As the most abundant of essential amino acids (EAAs), BCAAs are not only the substrates for synthesis of nitrogenous compounds, they also serve as signaling molecules regulating metabolism of glucose, lipid, and protein synthesis, intestinal health, and immunity via special signaling network, especially phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29563162/mtor-independent-alteration-in-ulk1-ser758-phosphorylation-following-chronic-lrrk2-kinase-inhibition
#10
Claudia Manzoni, Adamantios Mamais, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, Rosella Abeti, Paola Giunti, John Hardy, Mark R Cookson, Sharon A Tooze, Patrick A Lewis
Unc-51 Like Kinase 1 (ULK1) is a critical regulator of the biogenesis of autophagosomes, the central component of the catabolic macroautophagy pathway. Regulation of ULK1 activity is dependent upon several phosphorylation events acting to repress or activate the enzymatic function of this protein. Phosphorylation of Ser758 ULK1 has been linked to repression of autophagosome biogenesis and was thought to be exclusively dependent upon mTOR complex 1 kinase activity. In the present study, a novel regulation of Ser758 ULK1 phosphorylation is reported following prolonged inhibition of the Parkinson's disease linked protein leucine rich repeat kinase 2 (LRRK2)...
April 26, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29550128/increasing-the-availability-of-threonine-isoleucine-valine-and-leucine-relative-to-lysine-while-maintaining-an-ideal-ratio-of-lysine-methionine-alters-mammary-cellular-metabolites-mammalian-target-of-rapamycin-signaling-and-gene-transcription
#11
X Dong, Z Zhou, L Wang, B Saremi, A Helmbrecht, Z Wang, J J Loor
Amino acids not only serve as precursors for protein synthesis but also function as signaling molecules that can regulate the mammalian target of rapamycin (mTOR) pathway. Methionine and Lys are the most-limiting AA for milk production and a ratio of ∼3:1 Lys:Met in the metabolizable protein has been determined to be ideal. Besides Met and Lys, recent studies have evaluated Ile, Leu, Val, and Thr as potentially limiting for milk protein synthesis. The objective of this experiment was to determine if varying the ratio of Lys:Thr, Lys:Ile, Lys:Val, and Lys:Leu while maintaining an ideal ratio of Lys:Met and fixed ratio of other essential AA (IPAA) elicits changes in intracellular metabolites, gene transcription related to protein synthesis, and phosphorylation status of mTOR pathway proteins...
June 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29498661/the-regulatory-role-of-meaib-in-protein-metabolism-and-the-mtor-signaling-pathway-in-porcine-enterocytes
#12
Yulong Tang, Bie Tan, Guangran Li, Jianjun Li, Peng Ji, Yulong Yin
Amino acid transporters play an important role in cell growth and metabolism. MeAIB, a transporter-selective substrate, often represses the adaptive regulation of sodium-coupled neutral amino acid transporter 2 (SNAT2), which may act as a receptor and regulate cellular amino acid contents, therefore modulating cellular downstream signaling. The aim of this study was to investigate the effects of MeAIB to SNAT2 on cell proliferation, protein turnover, and the mammalian target of rapamycin (mTOR) signaling pathway in porcine enterocytes...
March 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29484383/the-transcription-factor-cmaf-is-targeted-by-mtor-and-regulates-the-inflammatory-response-via-the-tlr4-signaling-pathway
#13
Yan Wang, Caifu Luan, Guili Zhang, Chengming Sun
cMaf is a leucine-zipper transcription factor that is involved in cell differentiation, oncogenic transformation, and human diseases; however, the functions of cMaf in inflammatory responses in macrophages are still not fully understood. Western blot analysis showed that cMaf expression was induced by lipopolysaccharide (LPS) stimulation in mouse macrophages. An enzyme-linked immunosorbent assay was performed to detect the level of expression of inflammatory cytokines after knockdown of cMaf expression in macrophages using a small interfering RNA (siRNA)...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29444251/cultured-equine-satellite-cells-as-a-model-system-to-assess-leucine-stimulated-protein-synthesis-in-horse-muscle
#14
Michelle L DeBoer, Krishona M Martinson, Mary S Pampusch, Abigail M Hansen, Scott M Wells, Christie Ward, Marcia Hathaway
Leucine has been shown to stimulate the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway which plays numerous key regulatory roles in cell growth, survival, and metabolism including protein synthesis in a number of species. However, previous work with equine satellite cells has suggested distinct species differences in regards to physiological effects and the magnitude of responses to growth factors and regulators. Because there is limited research available regarding the role of leucine in regulating equine skeletal muscle protein synthesis, the objective of this study was to evaluate the effect of leucine on the mTOR signaling pathway in cultured equine satellite...
February 15, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29425714/leucyl-trna-synthetase-is-required-for-the-myogenic-differentiation-of-c2c12-myoblasts-but-not-for-hypertrophy-or-metabolic-alteration-of-myotubes
#15
Yoriko Sato, Yusuke Sato, Reiko Suzuki, Kodwo Obeng, Fumiaki Yoshizawa
Mammalian target of rapamycin (mTOR) signaling controls skeletal muscle cell differentiation, growth, and metabolism by sensing the intracellular energy status and nutrients. Recently, leucyl-tRNA synthetase (Lars) was identified as an intracellular sensor of leucine involved in the activation of mTOR signaling. However, there is still no evidence for the activation of mTOR signaling by Lars and its physiological roles in skeletal muscle cells. In this study, we determined the potential roles of Lars for the activation of mTOR signaling, skeletal muscle cell differentiation, hypertrophy, and metabolism using small interfering (si)-RNA knockdown...
March 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29422900/role-of-slc7a5-in-metabolic-reprogramming-of-human-monocyte-macrophage-immune-responses
#16
Bo Ruem Yoon, Yoon-Jeong Oh, Seong Wook Kang, Eun Bong Lee, Won-Woo Lee
Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activated T cells. However, the dynamics and relevance of SLC7A5 activity in monocytes/macrophages is still poorly understood. We provide evidence that SLC7A5-mediated leucine influx contributes to pro-inflammatory cytokine production via mTOR complex 1 (mTORC1)-induced glycolytic reprograming in activated human monocytes/macrophages...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29368944/a-specific-amino-acid-formula-prevents-alcoholic-liver-disease-in-rodents
#17
Laura Tedesco, Giovanni Corsetti, Chiara Ruocco, Maurizio Ragni, Fabio Rossi, Michele O Carruba, Alessandra Valerio, Enzo Nisoli
Chronic alcohol consumption promotes mitochondrial dysfunction, oxidative stress, defective protein metabolism, and fat accumulation in hepatocytes (liver steatosis). Inadequate amino-acid metabolism is worsened by protein malnutrition, frequently present in alcohol-consuming patients, with reduced circulating branched-chain amino acids (BCAAs). Here we asked whether dietary supplementation with a specific amino-acid mixture, enriched in BCAAs (BCAAem) and able to promote mitochondrial function in muscle of middle-aged rodents, would prevent mitochondrial dysfunction and liver steatosis in Wistar rats fed on a Lieber-DeCarli ethanol (EtOH)-containing liquid diet...
January 25, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29329236/gender-associated-impact-of-early-leucine-supplementation-on-adult-predisposition-to-obesity-in-rats
#18
Nora López, Juana Sánchez, Andreu Palou, Francisca Serra
Early nutrition plays an important role in development and may constitute a relevant contributor to the onset of obesity in adulthood. The aim of this study was to evaluate the long-term impact of maternal leucine (Leu) supplementation during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was supplied during lactation (21 days) and, from weaning onwards, was replaced by a standard chow diet. Then, at adulthood (6 months of age), this was replaced with hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content), for two months, to induce obesity...
January 12, 2018: Nutrients
https://www.readbyqxmd.com/read/29227681/%C3%AE-hydroxy-%C3%AE-methyl-butyrate-is-more-potent-than-leucine-in-inhibiting-starvation-induced-protein-degradation-in-c2c12-myotubes
#19
Yehui Duan, Fengna Li, Qiuping Guo, Wenlong Wang, Lingyu Zhang, Chaoyue Wen, Xiao'an Chen, Yulong Yin
Leucine (Leu) and its metabolites α-ketoisocaproate (KIC) and β-hydroxy-β-methyl butyrate (HMB) are potent regulators of protein turnover. The aim of this study was to compare the inhibitory effects of Leu, KIC, and HMB on protein degradation and to investigate the mechanisms involved. The results showed that the inhibitory effect of HMB (0.38 ± 0.04) was more potent than that of Leu (0.76 ± 0.04) and KIC (0.56 ± 0.04, P < 0.01), and was significantly abolished in the presence of LY294002 (1.48 ± 0...
January 10, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#20
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
February 2018: Amino Acids
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