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Mitochondria AND mTOR

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https://www.readbyqxmd.com/read/28433710/down-regulation-of-islet-amyloid-polypeptide-expression-induces-death-of-human-annulus-fibrosus-cells-via-mitochondrial-and-death-receptor-pathways
#1
Xinghuo Wu, Kun Wang, Wenbin Hua, Shuai Li, Xianzhe Liu, Wei Liu, Yu Song, Yukun Zhang, Zengwu Shao, Cao Yang
Islet amyloid polypeptide (IAPP) exerts its biological effects by participating in the regulation of glucose metabolism and cell apoptosis. The main goal of the present study was to investigate the expression of IAPP in degenerated intervertebral disc tissue and IAPP's modulation of extracellular matrix (ECM) catabolic and anabolic genes in human AF cells. We found that the expression of IAPP, the calcitonin receptor, and receptor activity modifying protein decreased considerably in AF cells during the progression of intervertebral disc degeneration (IDD)...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28428083/the-roles-of-subcellularly-located-egfr-in-autophagy
#2
REVIEW
Hongsen Li, Liangkun You, Jiansheng Xie, Hongming Pan, Weidong Han
The epidermal growth factor receptor (EGFR) is a well-studied receptor-tyrosine kinase that serves vital roles in regulation of organ development and cancer progression. EGFR not only exists on the plasma membrane, but also widely expressed in the nucleus, endosomes, and mitochondria. Most recently, several lines of evidences indicated that autophagy is regulated by EGFR in kinase-active and -independent manners. In this review, we summarized recent advances in our understanding of the functions of different subcellularly located EGFR on autophagy...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#3
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396174/sirt3-confers-protection-against-neuronal-ischemia-by-inducing-autophagy-involvement-of-the-ampk-mtor-pathway
#4
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/28386317/alisertib-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-mediated-pathways-in-human-glioblastoma-cells
#5
Zheng Liu, Feng Wang, Zhi-Wei Zhou, He-Chun Xia, Xin-Yu Wang, Yin-Xue Yang, Zhi-Xu He, Tao Sun, Shu-Feng Zhou
Glioblastoma (GBM) is the most common brain tumor with poor response to current therapeutics. Alisertib (ALS), a second-generation selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects on solid tumors in animal studies. This study aimed to investigate the killing effect of ALS on GBM cell line DAOY and the possible underlying mechanisms using both bioinformatic and cell-based approaches. Our molecular docking showed that ALS preferentially bound AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28353662/black-tea-high-molecular-weight-polyphenol-rich-fraction-promotes-hypertrophy-during-functional-overload-in-mice
#6
Yuki Aoki, Tetsuo Ozawa, Tohru Takemasa, Osamu Numata
Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5' adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample "E80" from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0...
March 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28333151/fto-is-required-for-myogenesis-by-positively-regulating-mtor-pgc-1%C3%AE-pathway-mediated-mitochondria-biogenesis
#7
Xiaobo Wang, Ning Huang, Min Yang, Dandan Wei, Haoran Tai, Xiaojuan Han, Hui Gong, Jiao Zhou, Jianqiong Qin, Xiawei Wei, Honghan Chen, Tingting Fang, Hengyi Xiao
Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28283188/targeted-cytoplasmic-irradiation-and-autophagy
#8
Jinhua Wu, Bo Zhang, Yen-Ruh Wuu, Mercy M Davidson, Tom K Hei
The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis...
March 1, 2017: Mutation Research
https://www.readbyqxmd.com/read/28238805/pharmacological-inhibition-of-lsd1-and-mtor-reduces-mitochondrial-retention-and-associated-ros-levels-in-the-red-blood-cells-of-sickle-cell-disease
#9
Ramasamy Jagadeeswaran, Benjamin A Vazquez, Muthusamy Thiruppathi, Balaji B Ganesh, Vinzon Ibanez, Shuaiying Cui, James D Engel, Alan M Diamond, Robert E Molokie, Joseph DeSimone, Donald Lavelle, Angela Rivers
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis...
February 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#10
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With the aim of evaluating anticancerous activities of 10-gingerol (10-G) against HeLa cells, it was purified and identified from "Tongling white ginger" by HSCCC, UPLC-TOF-MS/MS, and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity, and arrested cell cycle in the G0/G1 phase. Most cell cycle related genes and protein expression significantly decreased, followed by a slight decrease in a few without affecting cyclin B1 and cyclin E1 (protein)...
March 1, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28187451/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#11
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#12
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28161373/post-onset-oral-rapamycin-treatment-delays-development-of-mitochondrial-encephalopathy-only-at-supramaximal-doses
#13
Roberta Felici, Daniela Buonvicino, Mirko Muzzi, Leonardo Cavone, Daniele Guasti, Andrea Lapucci, Sara Pratesi, Francesco De Cesaris, Francesca Luceri, Alberto Chiarugi
Mitochondrial encephalopathies are fatal, infantile neurodegenerative disorders caused by a deficit of mitochondrial functioning, for which there is urgent need to identify efficacious pharmacological treatments. Recent evidence shows that rapamycin administered both intraperitoneally or in the diet delays disease onset and enhances survival in the Ndufs4 null mouse model of mitochondrial encephalopathy. To delineate the clinical translatability of rapamycin in treatment of mitochondrial encephalopathy, we evaluated the drug's effects on disease evolution and mitochondrial parameters adopting treatment paradigms with fixed daily, oral doses starting at symptom onset in Ndufs4 knockout mice...
February 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28143890/localization-of-mtorc2-activity-inside-cells
#14
Michael Ebner, Benjamin Sinkovics, Magdalena Szczygieł, Daniela Wolfschoon Ribeiro, Ivan Yudushkin
Activation of protein kinase Akt via its direct phosphorylation by mammalian target of rapamycin (mTOR) complex 2 (mTORC2) couples extracellular growth and survival cues with pathways controlling cell growth and proliferation, yet how growth factors target the activity of mTORC2 toward Akt is unknown. In this study, we examine the localization of the obligate mTORC2 component, mSin1, inside cells and report the development of a reporter to examine intracellular localization and regulation by growth factors of the endogenous mTORC2 activity...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28135838/novel-role-of-the-mitochondrial-protein-fus1-in-protection-from-premature-hearing-loss-via-regulation-of-oxidative-stress-and-nutrient-and-energy-sensing-pathways-in-the-inner-ear
#15
Winston J T Tan, Lei Song, Morven Graham, Amy Schettino, Dhasakumar Navaratnam, Wendell G Yarbrough, Joseph Santos-Sacchi, Alla V Ivanova
AIMS: Acquired hearing loss is a worldwide epidemic that affects all ages. It is multifactorial in etiology with poorly characterized molecular mechanisms. Mitochondria are critical components in hearing. Here, we aimed to identify the mechanisms of mitochondria-dependent hearing loss using Fus1 KO mice, our novel model of mitochondrial dysfunction/oxidative stress. RESULTS: Using auditory brainstem responses (ABRs), we characterized the Fus1 KO mouse as a novel, clinically relevant model of age-related hearing loss (ARHL) of metabolic etiology...
March 9, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28121223/using-tuberous-sclerosis-complex-to-understand-the-impact-of-mtorc1-signaling-on-mitochondrial-dynamics-and-mitophagy-in-neurons
#16
Darius Ebrahimi-Fakhari, Afshin Saffari, Lara Wahlster, Mustafa Sahin
Constitutive activation of the MTOR pathway is a key feature of defects in the tuberous sclerosis complex and other genetic neurodevelopmental diseases, collectively referred to as MTORopathies. MTORC1 hyperactivity promotes anabolic cell functions such as protein synthesis, yet at the same time catabolic processes such as macroautophagy/autophagy are suppressed. Mitochondria are major substrates of autophagy; however, their role in MTORopathies remains largely undefined. Here, we review our recent study showing that several aspects of mitochondrial function, dynamics and turnover are critically impaired in neuronal models of TSC...
April 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28108310/autophagic-dysregulation-in-doxorubicin-cardiomyopathy
#17
REVIEW
Jordan J Bartlett, Purvi C Trivedi, Thomas Pulinilkunnil
Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although the majority of prior research have implicated nuclear and mitochondrial events to be an important etiological aspects of DOX cardiomyopathy, recent discoveries in autophagy have highlighted the renewed interest in the role of lysosome in DOX cardiomyopathy. Indeed, dysregulation of lysosomal autophagy is observed in pre-clinical models of DOX cardiotoxicity...
January 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28107184/tunneling-nanotubes-promote-intercellular-mitochondria-transfer-followed-by-increased-invasiveness-in-bladder-cancer-cells
#18
Jinjin Lu, Xiufen Zheng, Fan Li, Yang Yu, Zhong Chen, Zheng Liu, Zhihua Wang, Hua Xu, Weimin Yang
Intercellular transfer of organelles via tunneling nanotubes (TNTs) is a novel means of cell-to-cell communication. Here we demonstrate the existence of TNTs between co-cultured RT4 and T24 bladder cancer cells using light microscopy, fluorescence imaging, and scanning electron microscopy (SEM). Spontaneous unidirectional transfer of mitochondria from T24 to RT4 cells was detected using fluorescence imaging and flow cytometry. The distribution of mitochondria migrated from T24 cells was in good agreement with the original mitochondria in RT4 cells, which may imply mitochondrial fusion...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28091556/vegf-b-promotes-recovery-of-corneal-innervations-and-trophic-functions-in-diabetic-mice
#19
Guohu Di, Xiaowen Zhao, Xia Qi, Songmei Zhang, Lu Feng, Weiyun Shi, Qingjun Zhou
Vascular endothelial growth factor (VEGF)-B possesses the capacity of promoting injured peripheral nerve regeneration and restore their sensory and trophic functions. However, the contribution and mechanism of VEGF-B in diabetic peripheral neuropathy remains unclear. In the present study, we investigated the expression and role of VEGF-B in diabetic corneal neuropathy by using type 1 diabetic mice and cultured trigeminal ganglion (TG) neurons. Hyperglycemia attenuated the endogenous expression of VEGF-B in regenerated diabetic corneal epithelium, but not that of VEGF receptors in diabetic TG neurons and axons...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#20
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
March 2017: Free Radical Biology & Medicine
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