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Lactate AND mTOR

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https://www.readbyqxmd.com/read/29651246/lactone-component-from-ligusticum-chuanxiong-alleviates-myocardial-ischemia-injury-through-inhibiting-autophagy
#1
Gang Wang, Guoliang Dai, Jie Song, Maomao Zhu, Ying Liu, Xuefeng Hou, Zhongcheng Ke, Yuanli Zhou, Huihui Qiu, Fujing Wang, Nan Jiang, Xiaobin Jia, Liang Feng
The dysregulation of autophagy is associated with a series of cardiovascular diseases, such as myocardial ischemia injury. Lactone component from Ligusticum chuanxiong (LLC) is the major constituent of the traditional Chinese herb L. chuanxiong Hort., which has been reported to hold potential cardioprotective effects. In this study, to determine whether LLC protects the heart through regulation of autophagy, we explored the effects of LLC on cardioprotection and autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29621758/targeting-mtor-by-cz415-inhibits-head-and-neck-squamous-cell-carcinoma-cells
#2
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
BACKGROUND/AIMS: mTOR is an important therapeutic target for human head and neck squamous cell carcinoma (HNSCC). The current study tested the anti-HNSCC cell activity by a mTOR kinase inhibitor CZ415. METHODS: HNSCC cells were treated with CZ415. Cell death was tested by lactate dehydrogenase (LDH) assay and MTT assay. Cell proliferation was tested by BrdU ELISA assay and [H3] thymidine incorporation assay, with apoptosis assayed by the TUNEL staining. A Western blotting assay was applied to test autophagy-associated proteins, mTOR and signalings...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29589262/ocimum-basilicum-but-not-ocimum-gratissimum-present-cytotoxic-effects-on-human-breast-cancer-cell-line-mcf-7-inducing-apoptosis-and-triggering-mtor-akt-p70s6k-pathway
#3
Renan Gianoti Torres, Livia Casanova, Julia Carvalho, Mariah Celestino Marcondes, Sonia Soares Costa, Mauro Sola-Penna, Patricia Zancan
Breast cancer is the major cause of death by cancer in women worldwide and in spite of the many drugs for its treatment, there is still the need for novel therapies for its control. Ocimum species have been used by traditional medicine to control several diseases, including cancer. We have previously characterized the antidiabetic properties of the unfractionated aqueous leaf extracts of Ocimum basilicum (OB) and Ocimum gratissimum (OG), modulating glucose metabolism in diabetic mice. Since glucose metabolism is primordial for cancer cells survival, we hypothesized that these extracts are effective against cancer cells...
March 28, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29556372/3-epi-12%C3%AE-hydroxyfroside-a-new-cardenolide-induces-cytoprotective-autophagy-via-blocking-the-hsp90-akt-mtor-axis-in-lung-cancer-cells
#4
Yan Sun, Yong-Hao Huang, Feng-Ying Huang, Wen-Li Mei, Quan Liu, Cai-Chun Wang, Ying-Ying Lin, Canhua Huang, Yue-Nan Li, Hao-Fu Dai, Guang-Hong Tan
Rationale: Cardenolides have potential as anticancer drugs. 3'-epi-12β-hydroxyfroside (HyFS) is a new cardenolide structure isolated by our research group, but its molecular mechanisms remain poorly understood. This study investigates the relationship between its antitumor activities and autophagy in lung cancer cells. Methods: Cell growth and proliferation were detected by MTT, lactate dehydrogenase (LDH) release, 5-ethynyl-20-deoxyuridine (EDU) and colony formation assays. Cell apoptosis was detected by flow cytometry...
2018: Theranostics
https://www.readbyqxmd.com/read/29502357/qiliqiangxin-attenuates-hypoxia-induced-injury-in-primary-rat-cardiac-microvascular-endothelial-cells-via-promoting-hif-1%C3%AE-dependent-glycolysis
#5
Yanyan Wang, Xueting Han, Mingqiang Fu, Jingfeng Wang, Yu Song, Yuan Liu, Jingjing Zhang, Jingmin Zhou, Junbo Ge
Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre-treated with QL (0.5 mg/mL) and/or HIF-1α siRNA were cultured in a three-gas hypoxic incubator chamber (5% CO2 , 1% O2 , 94% N2 ) for 12 hours...
March 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29454865/inhibitory-effects-of-selenium-on-cadmium-induced-cytotoxicity-in-pc12-cells-via-regulating-oxidative-stress-and-apoptosis
#6
Kaniz Fatima Binte Hossain, Md Mostafizur Rahman, Md Tajuddin Sikder, Takeshi Saito, Toshiyuki Hosokawa, Masaaki Kurasaki
Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (Na2 SeO3 ; Se4+ ) against cadmium (CdCl2 ; Cd2+ )-induced cytotoxicity using PC12 cells. In addition, Se (5, 10, 20 and 40 μM) and Cd (2.5, 5 and 10 μM)-induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (≥10 μM) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 μM) and toxic Cd (5 μM) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 μM) cells alone...
February 15, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29435722/l-arginine-regulates-protein-turnover-in-porcine-mammary-epithelial-cells-to-enhance-milk-protein-synthesis
#7
Qingquan Ma, Shengdi Hu, Makoto Bannai, Guoyao Wu
Milk is an important food for mammalian neonates, but its insufficient production is a nutritional problem for humans and other animals. Recent studies indicate that dietary supplementation with L-arginine (Arg) increases milk production in mammals, including sows, rabbits, and cows. However, the underlying molecular mechanisms remain largely unknown. The present study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that Arg enhances milk protein synthesis via activation of the mechanistic target of rapamycin (mTOR) cell signaling...
February 12, 2018: Amino Acids
https://www.readbyqxmd.com/read/29420538/th-pok-regulates-mammary-gland-lactation-through-mtor-srebp-pathway
#8
Rui Zhang, Huimin Ma, Yuan Gao, Yanjun Wu, Yuemei Qiao, Ajun Geng, Cheguo Cai, Yingying Han, Yi Arial Zeng, Xiaolong Liu, Gaoxiang Ge
The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner...
February 8, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29413509/evaluation-of-the-clinical-characteristics-of-everolimus-induced-lung-injury-and-determination-of-associated-risk-factors
#9
Mitsuhiro Abe, Kenji Tsushima, Jun Ikari, Naoko Kawata, Jiro Terada, Nobuhiro Tanabe, Koichiro Tatsumi
BACKGROUND: Everolimus (ERL), a mammalian target of rapamycin (mTOR) inhibitor, has been used for the management of several advanced cancers. ERL frequently causes lung injury, although the clinical and radiographic features have not been clarified. The aim of this study was to assess the clinical features of ERL-induced lung injury and determine the associated risk factors. METHODS: This single-center, retrospective study included 45 patients (29 men, 16 women; age, 12-78 years) who had received ERL at our hospital between August 2010 and March 2016...
January 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29384225/jolkinolide-b-inhibits-glycolysis-by-downregulating-hexokinase-2-expression-through-inactivating-the-akt-mtor-pathway-in-non-small-cell-lung-cancer-cells
#10
Xiang Gao, Han Han
Jolkinolide B (JB), a bioactive compound isolated from herbal medicine, has been found to inhibit tumor growth by altering glycolysis. However, whether glycolysis is influenced by JB in non-small cell lung cancer (NSCLC) cells and the mechanism remain unknown. The aim of the present study was to evaluate the effect of JB on the glycolysis in NSCLC cells and the underlying molecular mechanism. The results showed that JB treatment inhibited cell viability of A549 and H1299 cells in a concentration-dependent manner...
January 31, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29364854/cytoprotective-mechanisms-in-fatty-liver-preservation-against-cold-ischemia-injury-a-comparison-between-igl-1-and-htk
#11
Arnau Panisello-Roselló, Eva Verde, Alexandre Lopez, Marta Flores, Emma Folch-Puy, Anabela Rolo, Carlos Palmeira, Georgina Hotter, Teresa Carbonell, René Adam, Joan Roselló-Catafau
Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions...
January 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13-c-lactate
#12
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina DiGialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan R Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials, and this study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the cellular metabolism of prostate cancer cells. We observed a reduction in cell motility and aerobic glycolysis in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes and transporters involved in glycolysis...
March 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329236/gender-associated-impact-of-early-leucine-supplementation-on-adult-predisposition-to-obesity-in-rats
#13
Nora López, Juana Sánchez, Andreu Palou, Francisca Serra
Early nutrition plays an important role in development and may constitute a relevant contributor to the onset of obesity in adulthood. The aim of this study was to evaluate the long-term impact of maternal leucine (Leu) supplementation during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was supplied during lactation (21 days) and, from weaning onwards, was replaced by a standard chow diet. Then, at adulthood (6 months of age), this was replaced with hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content), for two months, to induce obesity...
January 12, 2018: Nutrients
https://www.readbyqxmd.com/read/29324300/hippocampal-insulin-resistance-links-maternal-obesity-with-impaired-neuronal-plasticity-in-adult-offspring
#14
Lisa Schmitz, Rebecca Kuglin, Inga Bae-Gartz, Ruth Janoschek, Sarah Appel, Andrea Mesaros, Igor Jakovcevski, Christina Vohlen, Marion Handwerk, Regina Ensenauer, Jörg Dötsch, Eva Hucklenbruch-Rother
OBJECTIVE: Maternal obesity and a disturbed metabolic environment during pregnancy and lactation have been shown to result in many long-term health consequences for the offspring. Among them, impairments in neurocognitive development and performance belong to the most dreaded ones. So far, very few mechanistic approaches have aimed to determine the responsible molecular events. METHODS: In a mouse model of maternal diet-induced obesity and perinatal hyperinsulinemia, we assessed adult offspring's hippocampal insulin signaling as well as concurrent effects on markers of hippocampal neurogenesis, synaptic plasticity and function using western blotting and immunohistochemistry...
March 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29323924/akt-serine-threonine-kinase-1-regulates-de-novo-fatty-acid-synthesis-through-the-mammalian-target-of-rapamycin-sterol-regulatory-element-binding-protein-1-axis-in-dairy-goat-mammary-epithelial-cells
#15
Tianying Zhang, Jiangtao Huang, Yongqing Yi, Xueying Zhang, Juan J Loor, Yanhong Cao, Huaiping Shi, Jun Luo
Akt serine/threonine kinase acts as a central mediator in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, regulating a series of biological processes. In lipid metabolism, Akt activation regulates a series of gene expressions, including genes related to intracellular fatty acid synthesis. However, the regulatory mechanisms of Akt in dairy goat mammary lipid metabolism have not been elaborated. In this study, the coding sequences of goat Akt1 gene were cloned and analyzed. Gene expression of Akt1 in different lactation stages was also investigated...
February 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29302579/myricetin-inhibits-angiogenesis-by-inducing-apoptosis-and-suppressing-pi3k-akt-mtor-signaling-in-endothelial-cells
#16
Gi Dae Kim
Background: Myricetin has been shown to possess potential antiangiogenic effects in endothelial cells. However, the underlying mechanisms are not fully understood. Therefore, we evaluated its antiangiogenic effects in human umbilical vascular endothelial cells (HUVECs). Methods: HUVECs were cultured in endothelial cell growth medium-2 to induce proliferation and angiogenesis and treated with different doses of myricetin (0.25, 0.5, and 1 μM) for 24 hours. Cell proliferation was analyzed by the MTT and lactate dehydrogenase release assays; angiogenesis was determined by the tube formation assay...
December 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29299135/acquired-resistance-to-pi3k-mtor-inhibition-is-associated-with-mitochondrial-dna-mutation-and-glycolysis
#17
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235. Monoclonal cells with stable and increased resistance to BEZ235 were obtained after 8 months treatment. These AQR clones showed class-specific resistance to PI3K/mTOR inhibitors, reduced G1 cell cycle arrest and impedance of migration following PI3K/mTOR inhibition, reduced PTEN expression and increased Akt and S6RP phosphorylation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273412/versatility-of-microglial-bioenergetic-machinery-under-starving-conditions
#18
Adam M Nagy, Rebeka Fekete, Gergo Horvath, Gabor Koncsos, Csilla Kriston, Anna Sebestyen, Zoltan Giricz, Zsuzsanna Kornyei, Emilia Madarasz, Laszlo Tretter
Microglia are highly dynamic cells in the brain. Their functional diversity and phenotypic versatility brought microglial energy metabolism into the focus of research. Although it is known that microenvironmental cues shape microglial phenotype, their bioenergetic response to local nutrient availability remains unclear. In the present study effects of energy substrates on the oxidative and glycolytic metabolism of primary - and BV-2 microglial cells were investigated. Cellular oxygen consumption, glycolytic activity, the levels of intracellular ATP/ADP, autophagy, mTOR phosphorylation, apoptosis and cell viability were measured in the absence of nutrients or in the presence of physiological energy substrates: glutamine, glucose, lactate, pyruvate or ketone bodies...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29248224/varying-the-ratio-of-lys-met-while-maintaining-the-ratios-of-thr-phe-lys-thr-lys-his-and-lys-val-alters-mammary-cellular-metabolites-mammalian-target-of-rapamycin-signaling-and-gene-transcription
#19
X Dong, Z Zhou, B Saremi, A Helmbrecht, Z Wang, J J Loor
Amino acids are not only precursors for but also signaling molecules regulating protein synthesis. Regulation of protein synthesis via AA occurs at least in part by alterations in the phosphorylation status of mammalian target of rapamycin (mTOR) pathway proteins. Although the ideal profile of Lys:Met to promote milk protein synthesis during established lactation in dairy cows has been proposed to be 3:1, aside from being the most-limiting AA for milk protein synthesis, the role of Met in other key biologic pathways such as methylation is not well characterized in the bovine...
February 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#20
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
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