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target of rapamycin

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https://www.readbyqxmd.com/read/28938597/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#1
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937754/bi-functional-elastin-like-polypeptide-nanoparticles-bind-rapamycin-and-integrins-and-suppress-tumor-growth-in-vivo
#2
Jugal P Dhandhukia, Pu Shi, Santosh Peddi, Zhe Li, Suhaas Rayudu Aluri, Yaping Ju, Dab Brill, Wan Wang, Siti Janib, Yi-An Lin, Shuanglong Liu, Honggang Cui, John Andrew MacKay
Recombinant protein-polymer scaffolds such as Elastin-Like Polypeptides (ELPs) offer drug delivery opportunities including biocompatibility, monodispersity, and multi-functionality. We recently reported that fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses growth of breast cancer xenografts, and reduces side-effects observed with free drug controls. This new report significantly advances this carrier strategy by demonstrating the co-assembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains...
September 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28937626/aspalathin-reverts-doxorubicin-induced-cardiotoxicity-through-increased-autophagy-and-decreased-expression-of-p53-mtor-p62-signaling
#3
Rabia Johnson, Samukelisiwe Shabalala, Johan Louw, Abidemi Paul Kappo, Christo John Frederick Muller
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28936961/-effects-of-small-rna-interference-targeting-mammalian-target-of-rapamycin-on-paraquat-induced-pulmonary-fibrosis-in-rats
#4
Wenbin Yang, Xiaoqing Zhao, Ran Liang, Da Chen
OBJECTIVE: To investigate the effects of small RNA interference targeting mammalian target of rapamycin (mTOR) expression on paraquat-induced pulmonary fibrosis in rats. METHODS: Human embryonic kidney cells HEK-293 were cultured in vitro. The mTOR small interfering RNA (mTOR-siRNA) expression plasmid transfection lentivirus was constructed, and non-specific sequence plasmid with no homology to mTOR gene was set as the control. Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, paraquat model group, mTOR unrelated sequence group, and mTOR-siRNA group, with 18 rats in each group...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28935818/increased-mir-124-3p-in-microglial-exosomes-following-traumatic-brain-injury-inhibits-neuronal-inflammation-and-contributes-to-neurite-outgrowth-via-their-transfer-into-neurons
#5
Shan Huang, Xintong Ge, Jinwen Yu, Zhaoli Han, Zhenyu Yin, Ying Li, Fanglian Chen, Haichen Wang, Jianning Zhang, Ping Lei
Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28935770/crystal-structure-of-the-human-lysosomal-mtorc1-scaffold-complex-and-its-impact-on-signaling
#6
Mariana E G de Araujo, Andreas Naschberger, Barbara G Fürnrohr, Taras Stasyk, Theresia Dunzendorfer-Matt, Stefan Lechner, Stefan Welti, Leopold Kremser, Giridhar Shivalingaiah, Martin Offterdinger, Herbert H Lindner, Lukas A Huber, Klaus Scheffzek
LAMTOR (Late endosomal and lysosomal adaptor and mitogen activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) activator) also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag GTPases associated with the pentamer through their C-terminal domains, predefining the orientation for interaction with mTORC1...
September 21, 2017: Science
https://www.readbyqxmd.com/read/28935164/elevated-expression-of-neuropeptide-signaling-genes-in-the-eyestalk-ganglia-and-y-organ-of-gecarcinus-lateralis-individuals-that-are-refractory-to-molt-induction
#7
Natalie L Pitts, Hanna M Schulz, Stephanie R Oatman, Donald L Mykles
Molting is induced in decapod crustaceans via multiple leg autotomy (MLA) or eyestalk ablation (ESA). MLA removes five or more walking legs, which are regenerated and become functional appendages at ecdysis. ESA eliminates the primary source of molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), which suppress the production of molting hormones (ecdysteroids) from the molting gland or Y-organ (YO). Both MLA and ESA are effective methods for molt induction in Gecarcinus lateralis. However, some G...
September 18, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#8
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28933980/panduratin-a-prevents-tumor-necrosis-factor-alpha-induced-muscle-atrophy-in-l6-rat-skeletal-muscle-cells
#9
Bo-Kyung Sa, Changhee Kim, Mi-Bo Kim, Jae-Kwan Hwang
Panduratin A, a prenylated chalcone compound, has anti-obesity, anti-bacterial, anti-cancer, anti-inflammatory, and anti-oxidative activities. However, its preventive effect on muscle atrophy has not been studied. The purpose of this study was to evaluate the inhibitory effect of panduratin A on muscle atrophy and to investigate its molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-treated L6 rat skeletal muscle cells. Panduratin A restored the myotube diameter reduced by TNF-α. At the molecular level, panduratin A elevated phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway and stimulated the MyoD and myogenin mRNA expression decreased by TNF-α...
September 21, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28933590/rubcn-rubicon-and-egfr-regulate-lysosomal-degradative-processes-in-the-retinal-pigment-epithelium-rpe-of-the-eye
#10
Luis Muniz-Feliciano, Teresa A Doggett, Zhenqing Zhou, Thomas A Ferguson
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#11
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28930963/role-of-autophagy-and-its-molecular-mechanisms-in-mice-intestinal-tract-after-severe-burn
#12
Duan Y Zhang, Wei Qiu, PeiS Jin, Peng Wang, Yong Sun
BACKGROUND: Severe burn can lead to hypoxia/ischemia of intestinal mucosa. Autophagy is the process of intracellular degradation, which is essential for cell survival under stresses, such as hypoxia/ischemia and nutrient deprivation. The present study was designed to investigate whether there were changes in intestinal autophagy after severe burn in mice and further to explore the effect and molecular mechanisms of autophagy on intestinal injury. METHODS: This study includes three experiments...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28929674/-molecular-mechanisms-of-autophagy-in-regulating-renal-aging-and-interventional-effects-of-chinese-herbal-medicine
#13
REVIEW
Yue Tu, Wei Sun, Di-Ping Chen, Yi-Gang Wan, Wei Wu, Jian Yao
Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor β (TGF-β) play the important roles in renal aging...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28929213/to-finish-things-well-cysteine-methylation-ensures-selective-gtpase-membrane-localization-and-signalling
#14
REVIEW
José Cansado
Isoprenylcysteine-O-Carboxyl Methyltransferase (ICMT) catalyzes the final step in the prenylation process of different proteins including members of the Ras superfamily of GTPases. While cysteine methylation is essential in mammalian cells for growth, membrane association, and signalling by Ras and Rho GTPases, its role during signal transduction events in simple eukaryotes like yeasts appears irrelevant. By using a multidisciplinary approach our group has recently shown that, contrary to this initial assumption, in the fission yeast Schizosaccharomyces pombe ICMT activity encoded by the Mam4 gene is not only important to promote selective plasma membrane targeting of Ras and specific Rho GTPases, but also to allow precise downstream signalling to the mitogen-activated protein kinase and target of rapamycin pathways in response to diverse environmental cues...
September 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28928817/dichloroacetate-induces-protective-autophagy-in-esophageal-squamous-carcinoma-cells
#15
Hong-Yu Jia, He-Nan Wang, Feng-Yu Xia, Yan Sun, Hong-Li Liu, Li-Li Yan, Shan-Shan Li, Dong-Chun Jiang, Mei-Mei Xu
Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#16
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928082/mir-338-3p-confers-5-fluorouracil-resistance-in-p53-mutant-colon-cancer-cells-by-targeting-the-mammalian-target-of-rapamycin
#17
Jia Han, Jie Li, Kaijie Tang, Huahua Zhang, Bo Guo, Ni Hou, Chen Huang
Evidence demonstrate that p53 mutations and microRNAs (miRs) are important components of 5-FU resistance in colorectal cancer (CRC). miR-338-3p has been reported associated with cancer prognosis. However whether or not it influences chemotherapy sensitivity and the underlying mechanisms have not been elucidated. Here, three types of human colon cancer cell lines, HT29 (mutant p53), HCT116 (wild-type p53), and HCT116 p53(-/-) (deficient p53), were treated with 5-FU. We showed that expression of miR-338-3p was correlated with apoptosis and 5-FU resistance in colon cancer cells...
September 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28927274/fluoride-induced-autophagy-via-the-regulation-of-mtor-phosphorylation-in-mice-leydig-cells
#18
Jianhai Zhang, Yuchen Zhu, Yan Shi, Yongli Han, Chen Liang, Zhiyuan Feng, Heping Zheng, Michelle Eng, Jundong Wang
Abstracts:Fluoride is known to impair testicular functions and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity by both in vivo and in vitro Leydig cell models. Using Transmission Electron Microscopy (TEM) and Monodansylcadaverine (MDC) staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice...
September 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28927154/resistance-to-the-mtor-inhibitor-everolimus-is-reversed-by-the-downregulation-of-survivin-in-breast-cancer-cells
#19
Ludovica Taglieri, Francesca De Iuliis, Anna Giuffrida, Sabrina Giantulli, Ida Silvestri, Susanna Scarpa
Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer. However, not all patients are equally sensitive to RAD001 and certain patients develop resistance. Therefore, the present study analyzed the mechanisms involved in the resistance of breast cancer cells to RAD001 in order to identify a potential tool to overcome it. The effects of RAD001 on the inhibition of cell viability, on the induction of apoptosis and autophagy and on the regulation of survivin, an anti-apoptotic protein, were evaluated in two breast cancer cell lines: BT474 (luminal B) and MCF7 (luminal A)...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927113/inhibition-of-autophagy-potentiates-the-proliferation-inhibition-activity-of-microrna-7-in-human-hepatocellular-carcinoma-cells
#20
Yanna Wang, Qiaoling Wang, Jiqing Song
MicroRNAs (miRNAs/miRs) are important molecules that are able to regulate multiple cellular processes in cancer cells. miR-7 has been previously identified as a tumor suppressive miRNA in several types of cancer. The aim of the present study was to investigate whether miR-7 is able to regulate autophagy in hepatocellular carcinoma (HCC) cells. It was identified that miR-7 was significantly downregulated in tumor tissues compared with adjacent normal tissues. Overexpression of miR-7 inhibited cell proliferative activity, which was partially reversed by miR-7 inhibitor...
September 2017: Oncology Letters
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