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https://www.readbyqxmd.com/read/27902464/expression-of-rab1a-is-upregulated-in-human-lung-cancer-and-associated-with-tumor-size-and-t-stage
#1
Xinxin Wang, Feng Liu, Xiaoyu Qin, Tinglei Huang, Bo Huang, Yanjie Zhang, Bin Jiang
Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined...
November 29, 2016: Aging
https://www.readbyqxmd.com/read/27894091/preclinical-study-of-cinobufagin-as-a-promising-anti-colorectal-cancer-agent
#2
Xing-Sheng Lu, Yin-Biao Qiao, Ya Li, Bo Yang, Min-Bin Chen, Chun-Gen Xing
Here, we assessed the anti-colorectal cancer (CRC) cell activity of cinobufagin (CBG). We found that CBG exerted potent cytotoxic and anti-proliferative activity against CRC lines (HCT-116 and HT-29) and primary human CRC cells. Meanwhile, it activated apoptosis, and disrupted cell-cycle progression in the cells. At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891586/celastrol-attenuates-cadmium-induced-neuronal-apoptosis-via-inhibiting-ca-2-camkii-dependent-akt-mtor-pathway
#3
Ruijie Zhang, Yu Zhu, Xiaoqing Dong, Beibei Liu, Nana Zhang, Xiaoxue Wang, Lei Liu, Chong Xu, Shile Huang, Long Chen
Cadmium (Cd), an environmental and industrial pollutant, affects the nervous system and consequential neurodegenerative disorders. Recently we have shown that celastrol prevents Cd-induced neuronal cell death partially by suppressing Akt/mTOR pathway. However, the underlying mechanism remains to be elucidated. Here we show that celastrol attenuated Cd-elevated intracellular free calcium ([Ca(2+) ]i ) level and apoptosis in neuronal cells. Celastrol prevented Cd-induced neuronal apoptosis by inhibiting Akt-mediated mTOR pathway, as inhibition of Akt with Akt inhibitor X or ectopic expression of dominant negative Akt reinforced celastrol's prevention of Cd-induced phosphorylation of S6K1/4E-BP1 and cell apoptosis...
November 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27888418/suppression-of-mtor-signaling-pathway-promotes-bone-marrow-mesenchymal-stem-cells-differentiation-into-osteoblast-in-degenerative-scoliosis-in-vivo-and-in-vitro
#4
Yu Wang, Xiao-Dong Yi, Chun-De Li
To investigate the role of mTOR signaling pathway in bone marrow mesenchymal stem cells (BMSCs) differentiation into osteoblast in degenerative scoliosis (DS). The rat model of DS was established. Thirty-two Sprague-Dawley (SD) rats were selected and divided into the normal control group, the positive control group (normal rats injected with rapamycin), the negative control group (DS rats injected with PBS) and the experiment group (DS rats injected with rapamycin). H&E staining was performed to observe the osteogenesis of scoliosis...
November 25, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27888132/vitamin-e-deficiency-depressed-fish-growth-disease-resistance-and-the-immunity-and-structural-integrity-of-immune-organs-in-grass-carp-ctenopharyngodon-idella-referring-to-nf-%C3%AE%C2%BAb-tor-and-nrf2-signaling
#5
Jia-Hong Pan, Lin Feng, Wei-Dan Jiang, Pei Wu, Sheng-Yao Kuang, Ling Tang, Yong-An Zhang, Xiao-Qiu Zhou, Yang Liu
This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp...
November 22, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27888130/protective-role-of-phenylalanine-on-the-ros-induced-oxidative-damage-apoptosis-and-tight-junction-damage-via-nrf2-tor-and-nf-%C3%AE%C2%BAb-signalling-molecules-in-the-gill-of-fish
#6
Lin Feng, Wen Li, Yang Liu, Wei-Dan Jiang, Sheng-Yao Kuang, Jun Jiang, Ling Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the possible preventive effects of dietary phenylalanine (Phe) on antioxidant responses, apoptosis and tight junction protein transcription in the gills of young grass carp (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of Phe (3.4-16.8 g kg(-1)) for 8 weeks. The results showed that Phe deficiency induced protein oxidation and lipid peroxidation by decreasing the glutathione content and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in fish gill (P < 0...
November 22, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27879318/inactivation-of-raptor-mtorc1-signaling-in-osteoclasts-increases-bone-mass-by-inhibiting-osteoclast-differentiation-in-mice
#7
Qinggang Dai, Furong Xie, Yujiiao Han, Xuhui Ma, Siru Zhou, Lingyong Jiang, Weiguo Zou, Jun Wang
Mammalian target of rapamycin complex 1 (mTORC1) is involved in anabolic metabolism in both osteoblasts and chondrocytes, but the role of mTORC1 in osteoclast biology in vivo remains to be elucidated. In this study, we showed that deletion of regulatory-associated protein of mTOR (Raptor) in osteoclasts led to an increase in bone mass with decreased bone resorption. Raptor-deficient bone marrow-derived macrophages (BMMs) exhibited lower mTORC1-S6K1 signaling and retarded osteoclast differentiation as determined by the number of osteoclasts, TRAP activity and expression of osteoclast-specific genes...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27875531/loss-of-c9orf72-enhances-autophagic-activity-via-deregulated-mtor-and-tfeb-signaling
#8
Janet Ugolino, Yon Ju Ji, Karen Conchina, Justin Chu, Raja Sekhar Nirujogi, Akhilesh Pandey, Nathan R Brady, Anne Hamacher-Brady, Jiou Wang
The most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia is a hexanucleotide repeat expansion in C9orf72. Here we report a study of the C9orf72 protein by examining the consequences of loss of C9orf72 functions. Deletion of one or both alleles of the C9orf72 gene in mice causes age-dependent lethality phenotypes. We demonstrate that C9orf72 regulates nutrient sensing as the loss of C9orf72 decreases phosphorylation of the mTOR substrate S6K1. The transcription factor EB (TFEB), a master regulator of lysosomal and autophagy genes, which is negatively regulated by mTOR, is substantially up-regulated in C9orf72 loss-of-function animal and cellular models...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27846451/sar-study-of-5-alkynyl-substituted-quinazolin-4-3h-ones-as-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#9
Manman Wei, Xi Zhang, Xiang Wang, Zilan Song, Jian Ding, Ling-Hua Meng, Ao Zhang
PI3Kδ is a key component in the aberrant signaling transduction in B cell malignancy, therefore specific targeting PI3Kδ has become an attractive molecularly targeted therapy for chronic lymphocytic leukemia (CLL). Herein, we describe the discovery and optimization of a series of 5-alkynyl substituted PI3Kδ inhibitors based on the first FDA-approved inhibitor idelalisib. Compound 8d bearing the 1-morpholinohex-5-yn-1-one moiety as the C5-substituent was identified to have high potency against PI3Kδ (3.82 nM) and SU-DHL-6 cells (7...
November 9, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27845329/hyperconnectivity-of-prefrontal-cortex-to-amygdala-projections-in-a-mouse-model-of-macrocephaly-autism-syndrome
#10
Wen-Chin Huang, Youjun Chen, Damon T Page
Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten(+/-)), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten(+/-) mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits...
November 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27832967/kinetic-modelling-of-in-vitro-data-of-pi3k-mtor1-pten-enzymes-and-on-target-inhibitors-rapamycin-bez235-and-ly294002
#11
Alexey Goltsov, Ghassan Tashkandi, Simon P Langdon, David J Harrison, James L Bown
The phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin-1 (mTOR1) are two key targets for anti-cancer therapy. Predicting the response of the PI3K/AKT/mTOR1 signalling pathway to targeted therapy is made difficult because of network complexities. Systems biology models can help explore those complexities but the value of such models is dependent on accurate parameterisation. Motivated by a need to increase accuracy in kinetic parameter estimation, and therefore the predictive power of the model, we present a framework to integrate kinetic data from enzyme assays into a unified enzyme kinetic model...
November 8, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27827806/citrulline-directly-modulates-muscle-protein-synthesis-via-the-pi3k-mapk-4e-bp1-pathways-evidence-from-in-vivo-ex-vivo-and-in-vitro-studies
#12
Servane Le Plénier, Arthur Goron, Athanassia Sotiropoulos, Eliane Archambault, Chantal Guihenneuc, Stéphane Walrand, Jerome Salles, Marion Jourdan, Nathalie Neveux, Luc Cynober, Christophe Moinard
Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature consistently shows CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both inter-organ and intra-organ trafficking and metabolism, we combined three approaches: in vivo, ex vivo and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle...
November 8, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27821074/a-quantitative-transcriptomic-analysis-of-the-physiological-significance-of-mtor-signaling-in-goat-fetal-fibroblasts
#13
Yuting Fu, Xu Zheng, Xiaoyang Jia, Uyanga Binderiya, Yanfeng Wang, Wenlei Bao, Lili Bao, Keyu Zhao, Yu Fu, Huifang Hao, Zhigang Wang
BACKGROUND: Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that is a central regulator of cell growth and metabolism. CCI-779 is a specific inhibitor of the mTORC1 signaling pathway. RESULTS: We performed comparative transcriptome profiling on Inner Mongolia Cashmere goat fetal fibroblasts (GFbs) that were treated with CCI-779 and untreated cells. A total of 365 differentially expressed genes (DEGs) appeared between untreated and CCI-779-treated GFbs, with an FDR ≤0...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27780878/blocking-mammalian-target-of-rapamycin-alleviates-bladder-hyperactivity-and-pain-in-rats-with-cystitis
#14
Simin Liang, Jie Li, Xin Gou, Daihui Chen
BACKGROUND: Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. RESULTS: The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E-binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27780861/s6k1-mediated-phosphorylation-regulates-phosphatidylinositol-4-phosphate-5-kinase-type-i-%C3%AE-degradation-and-cell-invasion
#15
Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang
Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here, we show that p70S6K1 (S6K1), a downstream target of mTOR, phosphorylates PIPKIγ90 at T553 and S555, and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion...
October 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27764525/celastrol-prevents-cadmium-induced-neuronal-cell-death-by-blocking-mitochondrial-ros-inactivation-of-ampk-and-activation-of-mtor-pathway
#16
Ruijie Zhang, Nana Zhang, Hai Zhang, Chunxiao Liu, Xiaoqing Dong, Xiaoxue Wang, Yu Zhu, Chong Xu, Lei Liu, Sijun Yang, Shile Huang, Long Chen
BACKGROUND AND PURPOSE: Increasing evidence has suggested cadmium (Cd), as an inducer of reactive oxygen species (ROS), is a potential pathogenic factor in human neurodegenerative diseases. Thus, it is important to find effective interventions for Cd-induced oxidative stress in the central nervous system. The purpose of this study was to determine whether and how celastrol, a plant-derived triterpene, could mitigate Cd-induced ROS and cell death in neuronal cells. EXPERIMENTAL APPROACH: PC12, SH-SY5Y cells and primary murine neurons were chosen as a model to study celastrol neuroprotection against Cd-poisoning...
October 20, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27760613/-alterations-of-mtor-pathway-and-autophagy-in-early-type-2-diabetic-cardiomyopathy-in-rats
#17
X H Sun, M S Yin, Y L Mu
Objective: To investigate the alterations of mTOR signaling pathway and autophagy in the development of type 2 diabetes and early diabetic cardiomyopathy and to study their roles in pathogenesis of diabetic myocardium. Methods: A type 2 diabetes rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, experiment group of 2 weeks and experiment group of 4 weeks. Alterations of mTOR, p-mTOR, S6K1, Beclin-1 and LC3-Ⅱ expression in myocardium were determined by Western blot and immunohistochemistry...
October 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/27749759/restorative-mechanisms-regulating-protein-balance-in-skeletal-muscle-during-recovery-from-sepsis
#18
Kristen T Crowell, David I Soybel, Charles H Lang
Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced...
October 5, 2016: Shock
https://www.readbyqxmd.com/read/27743383/lncrna-gas5-inhibits-proliferation-and-progression-of-prostate-cancer-by-targeting-mir-103-through-akt-mtor-signaling-pathway
#19
Dong Xue, Cuixing Zhou, Hao Lu, Renfang Xu, Xianlin Xu, Xiaozhou He
In prior research, evidence has been found for a relation between low exposure of long non-coding RNAs (lncRNAs) and prostate tumor genesis. This study aims to clarify the underlying mechanisms of lncRNA GAS5 in prostate cancer (PCa). In total, 118 pairs of PCa tissues and matched adjacent non-tumor tissues were collected. Additionally, lncRNA GAS5 exposure levels were determined using RT-PCR and in situ hybridization. In addition, dual-luciferase report assay was performed to verify the target effect of lncRNA GAS5 on miR-103...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27705797/s6k1-is-required-for-increasing-skeletal-muscle-force-during-hypertrophy
#20
Manuela Marabita, Martina Baraldo, Francesca Solagna, Judith Johanna Maria Ceelen, Roberta Sartori, Hendrik Nolte, Ivan Nemazanyy, Stéphane Pyronnet, Marcus Kruger, Mario Pende, Bert Blaauw
Loss of skeletal muscle mass and force aggravates age-related sarcopenia and numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a major role in stimulating adult muscle growth; however, the functional role of its downstream mediators in vivo is unknown. Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its sensitivity to rapamycin...
October 4, 2016: Cell Reports
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