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https://www.readbyqxmd.com/read/28791373/downregulation-of-bzw2-inhibits-osteosarcoma-cell-growth-by-inactivating-the-akt-mtor-signaling-pathway
#1
Dong-Dong Cheng, Shi-Jie Li, Bin Zhu, Ting Yuan, Qing-Cheng Yang, Cun-Yi Fan
Osteosarcoma is the most common malignant bone tumor in adolescents. The function of basic leucine zipper and W2 domains 2 (BZW2) in tumor progression has been reported. However, the role and mechanisms of BZW2 in osteosarcoma remain to be determined. The aim of the present study was to reveal the expression and biological functions of BZW2 in osteosarcoma and to elucidate the proximal mechanisms underlying these functions. The expression of BZW2 in osteosarcoma tissues and cell lines was assessed by qRT-PCR, western blotting and immunohistochemistry...
August 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28771726/annexin-a2-positively-regulates-milk-synthesis-and-proliferation-of-bovine-mammary-epithelial-cells-through-the-mtor-signaling-pathway
#2
Minghui Zhang, Dongying Chen, Zhen Zhen, Jinxia Ao, Xiaohan Yuan, Xuejun Gao
Annexin A2 (AnxA2) has been shown to play multiple roles in growth, development and metabolism, but the functions of AnxA2 and the signaling pathways associated with AnxA2 are still not fully understood. In this study, we aim to reveal whether and how AnxA2 could be involved in milk synthesis and proliferation of bovine mammary epithelial cells (BMECs). Using gene function study approaches, we found that AnxA2 positively regulates PIP3 level, phosphorylation of mTOR and protein levels of SREBP-1c and Cyclin D1 leading to milk synthesis and cell proliferation...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28758352/fast-digestive-leucine-rich-soluble-milk-proteins-improve-muscle-protein-anabolism-and-mitochondrial-function-in-undernourished-old-rats
#3
Jérôme Salles, Audrey Chanet, Alexandre Berry, Christophe Giraudet, Véronique Patrac, Carla Domingues-Faria, Christophe Rocher, Christelle Guillet, Philippe Denis, Corinne Pouyet, Cécile Bonhomme, Pascale Le Ruyet, Yves Rolland, Yves Boirie, Stéphane Walrand
SCOPE: One strategy to manage malnutrition in older patients is to increase protein and energy intake. Here we evaluate the influence of protein quality during refeeding on improvement in muscle protein and energy metabolism. METHODS AND RESULTS: Twenty-month-old male rats (n = 40) were fed 50% of their spontaneous intake for 12 weeks to induce malnutrition, then refed ad libitum with a standard diet enriched with casein or soluble milk proteins (22%) for 4 weeks...
July 31, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28731988/roles-of-mitogen-activating-protein-kinase-kinase-kinase-kinase-3-map4k3-in-preterm-skeletal-muscle-satellite-cell-myogenesis-and-mammalian-target-of-rapamycin-complex-1-mtorc1-activation-regulation
#4
Chu-Yi Guo, Mu-Xue Yu, Jie-Min Dai, Si-Nian Pan, Zhen-Tong Lu, Xiao-Shan Qiu, Si-Qi Zhuang
BACKGROUND Preterm skeletal muscle genesis is a paradigm for myogenesis. The role of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cells myogenesis or its relationship to mammalian target of rapamycin complex 1 (mTORC1) activity have not been previously elaborated. MATERIAL AND METHODS Small interfering RNA (siRNA) interference technology was used to inhibit MAP4K3 expression. Leucine stimulation experiments were performed following MAP4K3-siRNA interference...
July 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28647331/combination-of-histidine-lysine-methionine-and-leucine-promotes-%C3%AE-casein-synthesis-via-the-mechanistic-target-of-rapamycin-signaling-pathway-in-bovine-mammary-epithelial-cells
#5
H N Gao, S G Zhao, N Zheng, Y D Zhang, S S Wang, X Q Zhou, J Q Wang
The ratio of different AA in the diets of cows is vital to improve milk protein yield. β-Casein is one of the important milk proteins with high nutritive value. However, the suitable ratio of essential amino acids (EAA) for the expression of β-casein in the immortalized bovine mammary epithelial cell line is not fully characterized. This study employed response surface methodology to determine the optimal ratio of His, Lys, Met, and Leu on β-casein expression level in vitro and clarified the effect of the 4 EAA on β-casein via the mechanistic target of rapamycin (mTOR) signaling pathway...
June 21, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#6
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28598238/nlrc3-regulates-cellular-proliferation-and-apoptosis-to-attenuate-the-development-of-colorectal-cancer
#7
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 biologic 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...
July 3, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
Neil R W Martin, Mark C Turner, Robert Farrington, Darren J Player, Mark 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 utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, 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 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM...
October 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28341273/branched-chain-amino-acids-enhance-cyst-development-in-autosomal-dominant-polycystic-kidney-disease
#17
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...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28341051/whey-protein-derived-exosomes-increase-protein-synthesis-and-hypertrophy-in-c2-c12-myotubes
#18
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
#19
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
#20
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
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