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https://www.readbyqxmd.com/read/28638350/branched-chain-amino-acid-ingestion-stimulates-muscle-myofibrillar-protein-synthesis-following-resistance-exercise-in-humans
#1
Sarah R Jackman, Oliver C Witard, Andrew Philp, Gareth A Wallis, Keith Baar, Kevin D Tipton
The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28633336/a278c-mutation-of-dihydropteridine-reductase-decreases-autophagy-via-mtor-signaling
#2
Qin Si, Sifan Sun, Yanting Gu
Dihydropteridine reductase (QDPR) plays an important role in the recycling of BH4 and is closely related to oxidative stress. We have previously reported that the overexpression of QDPR in human kidney HEK293T cells significantly protected against oxidative stress, and these beneficial effects were abolished by A278C mutation. To evaluate the effect of wild-type and mutant QDPR on autophagy and its mechanism in HEK293T cells, we constructed the wild-type and mutant QDPR expression plasmids and transfected them into HEK293T cells...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#3
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28625872/decreased-enteritis-resistance-ability-by-dietary-low-or-excess-levels-of-lipids-through-impairing-the-intestinal-physical-and-immune-barriers-function-of-young-grass-carp-ctenopharyngodon-idella
#4
Lin Feng, Pei-Jun Ni, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xu Tang, He-Qun Shi, Xiao-Qiu Zhou
The current study explores the hypothesis that low or excess levels of lipids decrease the enteritis resistance ability through impairing the intestinal physical and immune barrier function of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp with an average initial weight of 261.41 ± 0.53 g were fed diets containing six graded levels of lipids at 5.9, 21.4, 36.0, 50.2, 66.6 and 80.1 g/kg for 8 weeks. After that, a challenge trial was conducted by injection of Aeromonas hydrophila over 2 weeks...
June 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28623128/targeting-pi3k-akt-mtor-by-ly3023414-inhibits-human-skin-squamous-cell-carcinoma-cell-growth-in-vitro-and-in-vivo
#5
Ying Zou, Minggai Ge, Xuemin Wang
Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28588499/intake-of-a-ketone-ester-drink-during-recovery-from-exercise-promotes-mtorc1-signaling-but-not-glycogen-resynthesis-in-human-muscle
#6
Tijs Vandoorne, Stefan De Smet, Monique Ramaekers, Ruud Van Thienen, Katrien De Bock, Kieran Clarke, Peter Hespel
Purpose: Ketone bodies are energy substrates produced by the liver during prolonged fasting or low-carbohydrate diet. The ingestion of a ketone ester (KE) rapidly increases blood ketone levels independent of nutritional status. KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown. Methods: Eight healthy trained males participated in a randomized double-blind placebo-controlled crossover study. In each session, subjects undertook a bout of intense one-leg glycogen-depleting exercise followed by a 5-h recovery period during which they ingested a protein/carbohydrate mixture...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28574820/differentiation-capacities-of-skeletal-muscle-satellite-cells-in-lantang-and-landrace-piglets
#7
Chun-Qi Gao, Yin-Long Xu, Cheng-Long Jin, Xiao-Chao Hu, Hai-Chang Li, Guang-Xu Xing, Hui-Chao Yan, Xiu-Qi Wang
We isolated and cultured satellite cells (SCs) from the longissimus dorsi muscles of 1-day-old male Landrace and Lantang piglets to compare the SC differentiation capacity in the two breeds. Lantang piglets yielded more (P < 0.05) SCs per gram of muscle than Landrace piglets (5.2 ± 0.9×104 vs. 2.4 ± 0.2×104). Transcription of the differentiation markers myogenin and myosin heavy chain I (MyHC I) in the longissimus dorsi muscle was higher in Lantang than Landrace piglets (P < 0.05). Protein levels of myogenin (P < 0...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571990/optimal-ratios-of-essential-amino-acids-stimulate-%C3%AE-casein-synthesis-via-activation-of-the-mammalian-target-of-rapamycin-signaling-pathway-in-mac-t-cells-and-bovine-mammary-tissue-explants
#8
S S Li, J J Loor, H Y Liu, L Liu, A Hosseini, W S Zhao, J X Liu
Amino acids are the building blocks of proteins and serve as key molecular components upstream of the signaling pathways that regulate protein synthesis. The objective of this study was to systematically investigate the effect of essential AA ratios on milk protein synthesis in vitro and to elucidate some of the underlying mechanisms. Triplicate cultures of MAC-T cells and bovine mammary tissue explants (MTE) were incubated with the optimal AA ratio (OPAA; Lys:Met, 2.9:1; Thr:Phe, 1.05:1; Lys:Thr, 1.8:1; Lys:His, 2...
May 29, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28559962/icariside-ii-promotes-the-osteogenic-differentiation-of-canine-bone-marrow-mesenchymal-stem-cells-via-the-pi3k-akt-mtor-s6k1-signaling-pathways
#9
Guangming Luo, Biao Xu, Yuanliang Huang
The aim of the present study was to investigate the osteogenic effects of icariside II (ICSII) on canine bone marrow mesenchymal stem cells (BMSCs) and the pathways by which these effects were induced. BMSCs were cultured and expanded to the fourth passage. The proliferative effects of ICSII were assessed using the cell counting kit-8 (CCK-8) assay. The osteogenic response to ICSII in BMSCs in vitro was examined by alkaline phosphatase (ALP) activity assays and Alizarin red staining. Using Western blot assays and real-time PCR (RT-PCR), we examined the expression of osteogenetic proteins/genes...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28548969/transcriptome-profiling-in-preadipocytes-identifies-long-noncoding-rnas-as-sam68-targets
#10
Naomi Li, Steven Hébert, Jingwen Song, Claudia L Kleinman, Stéphane Richard
The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484242/regulation-of-chk1-by-mtor-contributes-to-the-evasion-of-dna-damage-barrier-of-cancer-cells
#11
Xinhui Zhou, Weijin Liu, Xing Hu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Oncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28475806/rapamycin-reduced-pulmonary-vascular-remodelling-by-inhibiting-cell-proliferation-via-akt-mtor-signalling-pathway-down-regulation-in-the-carotid-artery-jugular-vein-shunt-pulmonary-hypertension-rat-model
#12
Xiaofan Ma, Jianping Yao, Yuan Yue, Shangming Du, Han Qin, Jian Hou, Zhongkai Wu
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease. However, effective treatments for PAH are rare. This study aimed to investigate the inhibitory effects of rapamycin on PAH in the carotid artery-jugular vein (CA-JV) shunt PAH rat model as well as the mechanism underlying these effects. METHODS: Twenty-four Sprague-Dawley rats were randomized into the following 3 groups: a control group, a CA-JV shunt group and a treatment group...
May 4, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28461701/activation-of-a-novel-p70-s6-kinase-1-dependent-intracellular-cascade-in-the-basolateral-nucleus-of-the-amygdala-is-required-for-the-acquisition-of-extinction-memory
#13
T N Huynh, E Santini, E Mojica, A E Fink, B S Hall, R N Fetcho, L Grosenick, K Deisseroth, J E LeDoux, C Liston, E Klann
Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#14
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28410969/characterization-and-mechanism-of-phosphoinositide-3-kinases-pi3ks-members-in-insulin-induced-changes-of-protein-metabolism-in-yellow-catfish-pelteobagrus-fulvidraco
#15
Mei-Qin Zhuo, Yan-Xiong Pan, Kun Wu, Yi-Huan Xu, Zhi Luo
In the present study, seven phosphoinositide 3-kinase (PI3K) members (PI3KCa, PI3KCb, PI3KCd, PI3KCg, PI3KC2a, PI3KC2b and PI3KC3, respectively) were isolated and characterized from yellow catfish Pelteobagrus fulvidraco, and their roles in insulin-induced changes of protein metabolism were determined. These seven PI3Ks can be divided into three classes, class I (including PI3KCa, PI3KCb, PI3KCd and PI3KCg), class II (including PI3KC2a and PI3KC2b) and class III (only including PI3KC3). Compared with mammals, all of these members share similar domain structure...
April 11, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28406985/metformin-inhibited-esophageal-squamous-cell-carcinoma-proliferation-in-vitro-and-in-vivo-and-enhanced-the-anti-cancer-effect-of-cisplatin
#16
Feng Wang, Xianfei Ding, Tao Wang, Zhengzheng Shan, Jun Wang, Shaoxuan Wu, Yanyan Chi, Yana Zhang, Zhuan Lv, Liuxing Wang, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied...
2017: PloS One
https://www.readbyqxmd.com/read/28389629/inhibition-of-p70-s6-kinase-s6k1-activity-by-a77-1726-the-active-metabolite-of-leflunomide-induces-autophagy-through-tak1-mediated-ampk-and-jnk-activation
#17
Xiulong Xu, Jing Sun, Ruilong Song, Michelle E Doscas, Ashley J Williamson, Jingsong Zhou, Jun Sun, Xinan Jiao, Xiufan Liu, Yi Li
mTOR activation suppresses autophagy by phosphorylating ULK1 at S757 and suppressing its enzymatic activity. Here we report that feedback activation of mTOR in the PI-3 kinase pathway by two p70 S6 kinase (S6K1) inhibitors (PF-4708671 and A77 1726, the active metabolite of an immunosuppressive drug leflunomide) or by S6K1 knockdown did not suppress but rather induced autophagy. Suppression of S6K1 activity led to the phosphorylation and activation of AMPK, which then phosphorylated ULK1 at S555. While mTOR feedback activation led to increased phosphorylation of ULK1 at S757, this modification did not the disrupt ULK1-AMPK interaction nor dampen ULK1 S555 phosphorylation and the induction of autophagy...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28366631/the-anti-hepatocellular-carcinoma-cell-activity-by-a-novel-mtor-kinase-inhibitor-cz415
#18
Wei Zhang, Bingyu Chen, Yu Zhang, Kaiqiang Li, Ke Hao, Luxi Jiang, Ying Wang, Xiaozhou Mou, Xiaodong Xu, Zhen Wang
Dysregulation of mammalian target of rapamycin (mTOR) in hepatocellular carcinoma (HCC) represents a valuable treatment target. Recent studies have developed a highly-selective and potent mTOR kinase inhibitor, CZ415. Here, we showed that nM concentrations of CZ415 efficiently inhibited survival and induced apoptosis in HCC cell lines (HepG2 and Huh-7) and primary-cultured human HCC cells. Meanwhile, CZ415 inhibited proliferation of HCC cells, more potently than mTORC1 inhibitors (rapamycin and RAD001). CZ415 was yet non-cytotoxic to the L02 human hepatocytes...
March 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342808/role-of-mtorc1-s6k1-signaling-pathway-in-regulation-of-hematopoietic-stem-cell-and-acute-myeloid-leukemia
#19
REVIEW
Joydeep Ghosh, Reuben Kapur
Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-p70 ribosomal protein kinase 1 (S6K1) signaling pathway occurs frequently in acute myeloid leukemia (AML) patients. This pathway also plays a critical role in maintaining normal cellular processes. Given the importance of leukemia stem cells (LSCs) in the development of minimal residual disease, it is critical to use therapeutic interventions that target the LSC population to prevent disease relapse. The mTORC1-S6K1 pathway has been identified as an important regulator of hematopoietic stem cell (HSC) and LSC functions...
March 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28340042/effects-of-dietary-l-arginine-levels-on-small-intestine-protein-turnover-and-the-expression-of-genes-related-to-protein-synthesis-and-proteolysis-of-layers
#20
L P Miao, C Yuan, X Y Dong, X Y Zhang, M Y Zhou, X T Zou
The aim of this study was to test the effects of dietary L-arginine (Arg) levels on protein turnover in the small intestine and the expression of genes related to protein synthesis and proteolysis of laying hens. Xinyang Black commercial laying hens (n = 864, aged 217 d) were randomly distributed to 6 treatments with 4 replicates of 36 birds. The dietary treatments were corn-corn gluten meal based diets containing 0.64, 0.86, 1.03, 1.27, 1.42 and 1.66% L-Arg, respectively. Fractional protein synthesis rate (FSR) and fractional protein gain rate (FGR) in the jejunum were the highest in the 1...
June 1, 2017: Poultry Science
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