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Lactate AND mTOR

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https://www.readbyqxmd.com/read/28497545/milk-protein-synthesis-is-regulated-by-t1r1-t1r3-a-g-protein-coupled-taste-receptor-through-the-mtor-pathway-in-the-mouse-mammary-gland
#1
Junqiang Liu, Yanhong Wang, Dewei Li, Yanhuan Wang, Menglu Li, Caifa Chen, Xingtang Fang, Hong Chen, Chunlei Zhang
SCOPE: Understanding the regulatory mechanism of milk protein synthesis is important to develop strategies to improve milk protein and enhance lactation performance. mTOR pathway is a crucial modulator of protein synthesis. In this study, we want to investigate if T1R1/T1R3 can regulate milk protein synthesis and mediate the mTOR pathway in the mice mammary gland in vivo. METHODS AND RESULTS: T1R1 knockout mice, WT mice, and mammary explants were used. The weigh-suckle-weigh method was used to quantify the milk yield...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28445971/stat3-regulates-glycolysis-via-targeting-hexokinase-2-in-hepatocellular-carcinoma-cells
#2
Man Li, Rui Jin, Weihua Wang, Tieying Zhang, Jiao Sang, Na Li, Qunying Han, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28434735/effects-of-graded-removal-of-lysine-from-an-intravenously-infused-amino-acid-mixture-on-lactation-performance-and-mammary-amino-acid-metabolism-in-lactating-goats
#3
C L Guo, Y T Li, X Y Lin, M D Hanigan, Z G Yan, Z Y Hu, Q L Hou, F G Jiang, Z H Wang
To investigate responses of milk protein synthesis and mammary AA metabolism to a graded decrease of postruminal Lys supply, 4 lactating goats fitted with jugular vein, mammary vein, and carotid artery catheters and transonic blood flow detectors on the external pudic artery were used in a 4 × 4 Latin square experiment. Goats were fasted for 24 h and then received a 9-h intravenous infusion of an AA mixture plus glucose. Milk yield was recorded and samples were taken in h 2 to 8 of the infusion period; a mammary biopsy was performed in the last hour...
April 20, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28426686/reactive-oxygen-species-are-required-for-driving-efficient-and-sustained-aerobic-glycolysis-during-cd4-t-cell-activation
#4
Dana M Previte, Erin C O'Connor, Elizabeth A Novak, Christina P Martins, Kevin P Mollen, Jon D Piganelli
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28420993/phellinus-linteus-mycelium-alleviates-myocardial-ischemia-reperfusion-injury-through-autophagic-regulation
#5
Hsing-Hui Su, Ya-Chun Chu, Jiuan-Miaw Liao, Yi-Hsin Wang, Ming-Shiou Jan, Chia-Wei Lin, Chiu-Yeh Wu, Chin-Yin Tseng, Jiin-Cherng Yen, Shiang-Suo Huang
The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#6
Xiao-Yu Chen, De-Fang Li, Ji-Chun Han, Bo Wang, Zheng-Ping Dong, Li-Na Yu, Zhao-Hai Pan, Chuan-Jun Qu, Ying Chen, Shi-Guo Sun, Qiu-Sheng Zheng
Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396174/sirt3-confers-protection-against-neuronal-ischemia-by-inducing-autophagy-involvement-of-the-ampk-mtor-pathway
#7
Shu-Hui Dai, Tao Chen, Xia Li, Kang-Yi Yue, Peng Luo, Li-Kun Yang, Jie Zhu, Yu-Hai Wang, Zhou Fei, Xiao-Fan Jiang
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis...
April 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28386017/multinuclear-nmr-and-mri-reveal-an-early-metabolic-response-to-mtor-inhibition-in-sarcoma
#8
Valentina Di Gialleonardo, Hannah N Aldeborgh, Vesselin Miloushev, Kelly M Folkers, Kristin Granlund, William D Tap, Jason S Lewis, Wolfgang A Weber, Kayvan Keshari
Biomarkers predicting rapalog responses in sarcomas where PI3K and mTOR are often hyperactivated could improve the suitable recruitment of responsive patients to clinical trials. PI3K/mTOR pathway activation drives energy production by regulating anaerobic glycolysis in cancer cells, suggesting a route toward a monitoring strategy. In this study, we took a multi-modality approach to evaluate the phenotypic effects and metabolic changes which occur with inhibition of the PI3K/mTOR pathway. Its central role in regulating glycolysis in human sarcomas was evaluated by short- and long-term rapamycin treatment in sarcoma cell lines...
April 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28363742/liraglutide-relieves-myocardial-damage-by-promoting-autophagy-via-ampk-mtor-signaling-pathway-in-zucker-diabetic-fatty-rat
#9
Ya Zhang, Yuanna Ling, Li Yang, Yanzhen Cheng, Pingzhen Yang, Xudong Song, Huixiong Tang, Yongkang Zhong, Lu Tang, Shangfei He, Shuangli Yang, Aihua Chen, Xianbao Wang
Liraglutide, a glucose-lowering agent used to treat type 2 diabetic mellitus is reported to exert cardioprotective effects in clinical trials and animal experiments. However, the cardioprotective mechanism of liraglutide on diabetic cardiomyopathy has not been fully illustrated. The present study was performed to investigate whether liraglutide alleviates diabetic myocardium injury by promoting autophagy and its underlying mechanisms. Our results show that liraglutide significantly reduced the levels of creatine kinase (CK) and lactate dehydrogenase (LDH), improved left ventricular functional status and alleviated myocardial fibrosis in the Zucker diabetic fatty (ZDF) rat model...
March 29, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28356345/mtor-activation-protects-liver-from-ischemia-reperfusion-induced-injury-through-nf-%C3%AE%C2%BAb-pathway
#10
Ziru Li, Jing Zhang, Michael Mulholland, Weizhen Zhang
Hepatic steatosis renders liver more vulnerable for ischemia/reperfusion injury (IRI), which commonly occurs in transplantation, trauma, and liver resection. The underlying mechanism is not fully characterized. We aimed to clarify the role of mechanistic target of rapamycin (mTOR) signaling in hepatic ischemia/reperfusion injury (HIRI) in normal and steatotic liver using Alb-TSC1(-/-) (AT) and Alb-mTOR(-/-) (Am) transgenic mice. Steatotic liver induced by high-fat diet was more vulnerable to IRI. Activation of hepatic mTOR in AT mice decreased lipid accumulation attenuated HIRI as measured by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, circulating levels of alanine aminotransferase and lactate dehydrogenase, and inflammatory mediators such as monocyte chemoattractant protein 1 (MCP-1), TNF-α, and IL-6 and hepatic cleaved caspase 3 in mice fed either a normal chow diet or a high-fat diet...
March 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28349530/the-antiproliferative-and-apoptotic-effects-of-apigenin-on-glioblastoma-cells
#11
Trevor A Stump, Brittany N Santee, Lauren P Williams, Rachel A Kunze, Chelsae E Heinze, Eric D Huseman, Rebecca J Gryka, Denise S Simpson, Samson Amos
OBJECTIVES: Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. METHODS: Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays...
March 28, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28346394/engineered-resistant-starch-ers-diet-shapes-colon-microbiota-profile-in-parallel-with-the-retardation-of-tumor-growth-in-in-vitro-and-in-vivo-pancreatic-cancer-models
#12
Concetta Panebianco, Kaarel Adamberg, Signe Adamberg, Chiara Saracino, Madis Jaagura, Kaia Kolk, Anna Grazia Di Chio, Paolo Graziano, Raivo Vilu, Valerio Pazienza
BACKGROUND/AIMS: Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model...
March 27, 2017: Nutrients
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#13
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317262/hydroxytyrosol-restores-proper-insulin-signaling-in-an-astrocytic-model-of-alzheimer-s-disease
#14
M Carmen Crespo, Joao Tomé-Carneiro, Cristina Pintado, Alberto Dávalos, Francesco Visioli, Emma Burgos-Ramos
Recent epidemiological evidence demonstrated that diabetes is a risk factor for AD onset and development. Indeed, meta-analyses of longitudinal epidemiologic studies show that diabetes increases AD risk by 50-100%, being insulin resistance (IR) the main binding link between diabetes and AD. Astrocytes are the foremost cerebral macroglial cells and are responsible for converting glucose into lactate and transfer it to neurons that use it as fuel, but Aβ(1-42) impairs insulin signaling and glycogen storage. Recent prospective studies showed that the Mediterranean diet is associated with lower incidence of AD...
March 20, 2017: BioFactors
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#15
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28290700/metabolic-response-to-everolimus-in-patient-derived-triple-negative-breast-cancer-xenografts
#16
Leslie R Euceda, Deborah K Hill, Endre Stokke, Rana Hatem, Rania El Botty, Ivan Bièche, Elisabetta Marangoni, Tone F Bathen, Siver A Moestue
Patients with triple-negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, the response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n = 103 animals)...
May 5, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28259993/glycometabolic-adaptation-mediates-the-insensitivity-of-drug-resistant-k562-adm-leukaemia-cells-to-adriamycin-via-the-akt-mtor-c-myc-signalling-pathway
#17
Xueyan Zhang, Ziying Ai, Jing Chen, Juan Yi, Zhuan Liu, Huaishun Zhao, Hulai Wei
In human leukaemia, resistance to chemotherapy leads to treatment ineffectiveness or failure. Previous studies have indicated that cancers with increased levels of aerobic glycolysis are insensitive to numerous forms of chemotherapy and respond poorly to radiotherapy. Whether glycolysis serves a key role in drug resistance of leukaemia cells remains unclear. The present study systematically investigated aerobic glycolytic alterations and regulation in K562/adriamycin (ADM) multidrug‑resistant (MDR) and ADM‑sensitive K562 leukaemia cells in normoxia, and the association between drug resistance and improper glycometabolism...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28237591/methionine-leucine-isoleucine-or-threonine-effects-on-mammary-cell-signaling-and-pup-growth-in-lactating-mice
#18
G M Liu, M D Hanigan, X Y Lin, K Zhao, F G Jiang, R R White, Y Wang, Z Y Hu, Z H Wang
Two studies were undertaken to assess the effects of individual essential AA supplementation of a protein-deficient diet on lactational performance in mice using litter growth rates as a response variable. The first study was designed to establish a dietary protein response curve, and the second to determine the effects of Leu, Ile, Met, and Thr supplementation of a protein-deficient diet on lactational performance. In both studies, dams were fed test diets from parturition through d 17 of lactation, when the studies ended...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28223230/myotoxicity-of-statins-mechanism-of-action
#19
REVIEW
Patrick du Souich, Ghislaine Roederer, Robert Dufour
Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations of statins in the myocyte and/or in presence of muscular conditions that may predispose to SIM. High concentrations of statins in the myocyte may occur whenever the activity of liver influx membrane transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular efflux transporters, MDR1 and BCRP, is reduced...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28219050/synergism-and-mechanism-of-astragaloside-iv-combined-with-ginsenoside-rg1-against-autophagic-injury-of-pc12-cells-induced-by-oxygen-glucose-deprivation-reoxygenation
#20
Xiao-Ping Huang, Huang Ding, Xiao-Qian Yang, Jing-Xian Li, Biao Tang, Xiao-Dan Liu, Ying-Hong Tang, Chang-Qing Deng
The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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