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leucine mtor

Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
Yuexin Wang, Ziru Li, Xinyu Zhang, Xinxin Xiang, Yin Li, Michael W Mulholland, Weizhen Zhang
Nesfatin-1, an 82 amino acid gastric peptide, is involved in regulation of food uptake and in multiple metabolic activities. Whether nesfatin-1 modulates the differentiation and lipid metabolism of brown adipocytes remains unknown. In the present study, we found that nesfatin-1 mRNA and protein were detectable in isolated brown adipocytes and gradually decreased during differentiation (95% CI 0.6057 to 1.034, p = 0.0001). The decrease in nesfatin-1 was associated with a significant reduction in p-S6. Exposure to nesfatin-1 promoted differentiation of brown adipocytes as revealed by a significant increase in UCP1 mRNA (p = 0...
November 8, 2016: Scientific Reports
Claudia Manzoni, Adamantios Mamais, Dorien A Roosen, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, John Hardy, Sharon A Tooze, Mark R Cookson, Patrick A Lewis
Leucine rich repeat kinase 2 is a complex enzyme with both kinase and GTPase activities, closely linked to the pathogenesis of several human disorders including Parkinson's disease, Crohn's disease, leprosy and cancer. LRRK2 has been implicated in numerous cellular processes; however its physiological function remains unclear. Recent reports suggest that LRRK2 can act to regulate the cellular catabolic process of macroautophagy, although the precise mechanism whereby this occurs has not been identified. To investigate the signalling events through which LRRK2 acts to influence macroautophagy, the mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) and Beclin-1/phosphatidylinositol 3-kinase (PI3K) pathways were evaluated in astrocytic cell models in the presence and absence of LRRK2 kinase inhibitors...
October 12, 2016: Scientific Reports
Laís Rosa Viana, Rafael Canevarolo, Anna Caroline Perina Luiz, Raquel Frias Soares, Camila Lubaczeuski, Ana Carolina de Mattos Zeri, Maria Cristina Cintra Gomes-Marcondes
BACKGROUND: Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia)...
October 3, 2016: BMC Cancer
Hideo Otsuki, Toru Kimura, Takashi Yamaga, Takeo Kosaka, Jun-Ichi Suehiro, Hiroyuki Sakurai
BACKGROUND: Leucine stimulates cancer cell proliferation through the mTOR pathway, therefore, inhibiting leucine transporters may be a novel therapeutic target for cancer. L-type amino acid transporter (LAT) 1, a Na(+) -independent amino acid transporter, is highly expressed in many tumor cells. However, leucine transporter(s) in different stages of prostate cancer, particularly in the stages of castration resistance with androgen receptor (AR) expression, is unclear. METHODS: LNCaP and DU145 and PC-3 cell lines were used as a model of androgen dependent, and metastatic prostate cancer...
October 3, 2016: Prostate
Liufeng Zheng, Wei Zhang, Yuanfei Zhou, Fengna Li, Hongkui Wei, Jian Peng
The mammalian target of rapamycin (mTOR) is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs), especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood...
2016: International Journal of Molecular Sciences
Jiangbo Wu, Caroline G M de Theije, Sofia Lopes da Silva, Suzanne Abbring, Hilma van der Horst, Laus M Broersen, Linette Willemsen, Martien Kas, Johan Garssen, Aletta D Kraneveld
Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs...
September 15, 2016: Brain, Behavior, and Immunity
Richard A Perry, Lemuel A Brown, David E Lee, Jacob L Brown, Jamie I Baum, Nicholas P Greene, Tyrone A Washington
The data described herein is related to the article "Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration" [1]. Aging is associated with a decreased ability of skeletal muscle to regenerate following injury. Leucine supplementation has been extensively shown, in young subjects, to promote protein synthesis during regeneration; however, the effects of leucine supplementation on the Akt/mTOR pathway in aged mice at the onset of muscle regeneration are not fully elucidated...
September 2016: Data in Brief
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Wei Wei, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1)...
2016: PloS One
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Hans-Bernd Rothenhäusler, Simon Theokas, Christoph Robier, Harald Mangge, Gerhard Reicht, Peter Hlade, Andreas Meinitzer
BACKGROUND: The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. METHODS: The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography...
2016: PloS One
Mee-Sup Yoon, Kook Son, Edwin Arauz, Jung Min Han, Sunghoon Kim, Jie Chen
Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation...
August 9, 2016: Cell Reports
Yasuhiro Ohshima, Kyoichi Kaira, Aiko Yamaguchi, Noboru Oriuchi, Hideyuki Tominaga, Shushi Nagamori, Yoshikatsu Kanai, Takehiko Yokobori, Tatsuya Miyazaki, Takayuki Asao, Yoshito Tsushima, Hiroyuki Kuwano, Noriko S Ishioka
System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth. In this study, we investigated the tumor-suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal cancer cell lines KYSE30 and KYSE150...
July 28, 2016: Cancer Science
Elitsa A Ananieva, Jonathan D Powell, Susan M Hutson
In connection with the increasing interest in metabolic regulation of the immune response, this review discusses current advances in understanding the role of leucine and leucine metabolism in T lymphocyte (T cell) activation. T cell activation during the development of an immune response depends on metabolic reprogramming to ensure that sufficient nutrients and energy are taken up by the highly proliferating T cells. Leucine has been described as an important essential amino acid and a nutrient signal that activates complex 1 of the mammalian target of rapamycin (mTORC1), which is a critical regulator of T cell proliferation, differentiation, and function...
July 2016: Advances in Nutrition
David D Church, Neil A Schwarz, Mike B Spillane, Sarah K McKinley-Barnard, Tom L Andre, Alejandro J Ramirez, Darryn S Willoughby
OBJECTIVE: Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise. METHODS: Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8-10 repetitions at 75%-80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises...
June 22, 2016: Journal of the American College of Nutrition
Richard A Perry, Lemuel A Brown, David E Lee, Jacob L Brown, Jamie I Baum, Nicholas P Greene, Tyrone A Washington
Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging alters skeletal muscle regeneration and leucine-induced alterations in markers of protein synthesis. The tibialis anterior of young (3 months) and aged (24 months) female C57BL/6J mice were injected with either bupivacaine or PBS, and the mice were given ad libitum access to leucine-supplemented or normal drinking water...
July 2016: Mechanisms of Ageing and Development
Guillermo Escalante, Michelle Alencar, Bryan Haddock, Phillip Harvey
BACKGROUND: Phosphatidic acid (PA) is a lipid messenger that has been shown to increase muscle protein synthesis via signaling stimulation of the mammalian target of rapamycin (mTOR). MaxxTOR® (MT) is a supplement that contains PA as the main active ingredient but also contains other synergistic mTOR signaling substances including L-Leucine, Beta-Hydroxy-Beta-Methylbutyrate (HMB), and Vitamin D3. METHODS: Eighteen healthy strength-trained males were randomly assigned to a group that either consumed MT (n = 8, 22...
2016: Journal of the International Society of Sports Nutrition
Zhang Xiao Ying, Meiyan Jin, Luke F Peterson, Denzil Bernard, Kamlai Saiya-Cork, Mehmet Yildiz, Shaomeng Wang, Mark S Kaminski, Alfred E Chang, Daniel J Klionsky, Sami N Malek
PURPOSE: This study was performed to further our understanding of the biological and genetic basis of follicular lymphoma and to identify potential novel therapy targets. EXPERIMENTAL DESIGN: We analyzed previously generated whole exome sequencing data of 23 follicular lymphoma cases and one transformed follicular lymphoma case and expanded findings to a combined total of 125 follicular lymphoma/3 transformed follicular lymphoma. We modeled the three-dimensional location of RRAGC-associated hotspot mutations...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nikolaj Rittig, Ermina Bach, Henrik H Thomsen, Andreas B Møller, Jakob Hansen, Mogens Johannsen, Erik Jensen, Anja Serena, Jens O Jørgensen, Bjørn Richelsen, Niels Jessen, Niels Møller
BACKGROUND: Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite β-hydroxy-β-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and whether common or separate intracellular signaling cascades are involved. OBJECTIVE: To compare a specific leucine-rich whey protein beverage (LWH) with isocaloric carbohydrate- (CHO), soy protein (SOY), and soy protein +3 g HMB (HMB) during fasting-induced catabolic conditions...
May 25, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Ming Ye, Yong-Feng Bi, Li Ding, Wei-Wei Zhu, Wei Gao
OBJECTIVE: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. METHODS: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1β and TNF-α were then determined...
July 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Elisabet Cuyàs, Salvador Fernández-Arroyo, Tomás Alarcón, Ruth Lupu, Jorge Joven, Javier A Menendez
We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human breast epithelial cells in which the knock-in of 185delAG mutation in a single BRCA1 allele leads to genomic instability. Mutant BRCA1 one-hit epithelial cells displayed constitutively enhanced activation of biosynthetic nodes within mitochondria...
May 31, 2016: Oncotarget
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