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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936683/trail-enhances-quinacrine-mediated-apoptosis-in-breast-cancer-cells-through-induction-of-autophagy-via-modulation-of-p21-and-dr5-interactions
#2
Sarita Das, Anmada Nayak, Sumit Siddharth, Deepika Nayak, Satya Narayan, Chanakya Nath Kundu
PURPOSE: Previously, we reported that quinacrine (QC) may cause apoptosis in breast and colon cancer cells by activating the death receptor 5 (DR5), resulting in autophagic cell death through p21 modulation. Here, we systematically evaluated the combined role of p21 and DR5 and their crosstalk in QC-mediated autophagy and apoptosis in breast cancer cells using in vitro and in vivo models. METHODS: Multiple breast cancer-derived cell lines (MCF-7, ZR-75-1, T47D, MDA-MB-231 and MCF-10A-Tr) and a mouse xenograft model were used...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28932706/global-proteomics-revealed-klebsiella-pneumoniae-induced-autophagy-and-oxidative-stress-in-caenorhabditis-elegans-by-inhibiting-pi3k-akt-mtor-pathway-during-infection
#3
Arumugam Kamaladevi, Krishnaswamy Balamurugan
The enterobacterium, Klebsiella pneumoniae invades the intestinal epithelium of humans by interfering with multiple host cell response. To uncover a system-level overview of host response during infection, we analyzed the global dynamics of protein profiling in Caenorhabditis elegans using quantitative proteomics approach. Comparison of protein samples of nematodes exposed to K. pneumoniae for 12, 24, and 36 h by 2DE revealed several changes in host proteome. A total of 266 host-encoded proteins were identified by 2DE MALDI-MS/MS and LC-MS/MS and the interacting partners of the identified proteins were predicted by STRING 10...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28929674/-molecular-mechanisms-of-autophagy-in-regulating-renal-aging-and-interventional-effects-of-chinese-herbal-medicine
#4
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/28929344/glucosidase-ii-beta-subunit-gluii%C3%AE-plays-a-role-in-autophagy-and-apoptosis-regulation-in-lung-carcinoma-cells-in-a-p53-dependent-manner
#5
Worapong Khaodee, Nichanan Inboot, Suruk Udomsom, Warunee Kumsaiyai, Ratchada Cressey
PURPOSE: Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins. Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis. Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells. METHODS: A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status...
September 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28927274/fluoride-induced-autophagy-via-the-regulation-of-mtor-phosphorylation-in-mice-leydig-cells
#6
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/28926094/curcumin-regulates-proliferation-autophagy-and-apoptosis-in-gastric-cancer-cells-by-affecting-pi3k-and-p53-signaling
#7
Hongbing Fu, Changming Wang, Dejun Yang, Xin Zhang, Ziran Wei, Zhenxin Zhu, Jiapeng Xu, Zunqi Hu, Yu Zhang, Weimin Wang, Ronglin Yan, Qingping Cai
In this study, we aimed to investigate the effects of curcumin on cell activities of gastric cancer (GC), and the connection between curcumin and P53 as well as PI3K signaling. This study was conducted with two cell lines SGC-7901 and BGC-823, both were exposed to curcumin at the concentrations of 0 µM, 10 µM, 20 µM and 40 µM. MTT assay, flow cytometry (FCM) assay, transmission electron microscopy (TEM) were used to study the underlying mechanisms of curcumin in respective of proliferation, apoptosis and autophagy...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28915718/the-pi3k-akt-pathway-a-critical-player-in-intervertebral-disc-degeneration
#8
REVIEW
Zhi-Hua Ouyang, Wen-Jun Wang, Yi-Guo Yan, Bing Wang, Guo-Hua Lv
Intervertebral disc degeneration (IDD) is thought to be the primary cause of low back pain, a severe public health problem worldwide. Current therapy for IDD aims to alleviate the symptoms and does not target the underlying pathological alternations within the disc. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway protects against IDD, which is attributed to increase of ECM content, prevention of cell apoptosis, facilitation of cell proliferation, induction or prevention of cell autophagy, alleviation of oxidative damage, and adaptation of hypoxic microenvironment...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#9
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915623/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#10
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903184/dexmedetomidine-exerts-neuroprotective-effect-via-the-activation-of-the-pi3k-akt-mtor-signaling-pathway-in-rats-with-traumatic-brain-injury
#11
Min Shen, Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Xiu-Min Zhou, Man-He Zhang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
OBJECTIVE: This study aims to explore the neuroprotective effects of dexmedetomidine (Dex) in rats suffering from traumatic brain injury (TBI) via the PI3K/Akt/mTOR signaling pathway. METHODS: A weight drop model was performed for TBI model establishment. A total of 150 Sprague Dawley rats were selected and assigned into control, sham, TBI, TBI+Dex, TBI+LY294002 (LY) and TBI+Dex+LY groups. Modified Neurological Severity Score (mNSS) was conducted in order to evaluate the neurological injury...
September 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28902711/triggering-of-inflammasome-by-impaired-autophagy-in-response-to-acute-experimental-parkinson-s-disease-involvement-of-the-pi3k-akt-mtor-pathway
#12
Sabrina Giacoppo, Placido Bramanti, Emanuela Mazzon
Several lines of evidence suggest that the inflammasome activation is involved in the progression of neurodegenerative diseases. However, the relation between Parkinson's disease (PD) and the inflammasome is still unclear. This study was designed to assess the involvement of inflammasome in acute experimental PD. Specifically, acute PD was induced in C57BL/6 mice by an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At seven days from MPTP induction, mice were euthanized and the midbrains were sampled to carry out immunohistochemical evaluations and western blot analysis...
September 11, 2017: Neuroreport
https://www.readbyqxmd.com/read/28894987/the-induction-of-apoptosis-and-autophagy-in-human-hepatoma-smmc-7721-cells-by-combined-treatment-with-vitamin-c-and-polysaccharides-extracted-from-grifola-frondosa
#13
Fei Zhao, Jin Zhao, Lei Song, Ya-Qing Zhang, Zhong Guo, Ke-Hu Yang
Polysaccharides extracted from the mushroom Grifola frondosa (GFP) are a potential anticancer agent. The objective of this study was to investigate the effect of GFP and vitamin C (VC) alone and in combination on the viability of human hepatocarcinoma SMMC-7721 and HepG2 cells. Studies designed to detect cell apoptosis and autophagy were also conducted to investigate the mechanism. Results from the cell viability assay indicated that a combination of GFP (0.2 or 0.25 mg/mL) and VC (0.3 mmol/L) (GFP/VC) led to 52...
September 11, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28889265/manganese-and-the-insulin-igf-signaling-network-in-huntington-s-disease-and-other-neurodegenerative-disorders
#14
Miles R Bryan, Aaron B Bowman
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28877265/niclosamide-induces-protein-ubiquitination-and-inhibits-multiple-pro-survival-signaling-pathways-in-the-human-glioblastoma-u-87-mg-cell-line
#15
Benxu Cheng, Liza Doreen Morales, Yonghong Zhang, Shizue Mito, Andrew Tsin
Glioblastoma is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. The anti-helminthic drug niclosamide, which has long been in use to treat tapeworm infections, has recently attracted renewed interest due to its apparent anticancer effects in a variety of in vitro and in vivo cancer models. However, the mechanism(s) of action remains to be elucidated. In the present study, we found that niclosamide induced cell toxicity in human glioblastoma cells corresponding with increased protein ubiquitination, ER stress and autophagy...
2017: PloS One
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#16
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28871076/knockdown-of-microrna-122-protects-h9c2-cardiomyocytes-from-hypoxia-induced-apoptosis-and-promotes-autophagy
#17
Zaiwei Zhang, Hu Li, Shasha Chen, Ying Li, Zhiyuan Cui, Jie Ma
BACKGROUND Acute myocardial infarction (AMI) is a severe disease causing heart failure and sudden death. Studies indicate that microRNAs (miRNAs) are involved in the pathophysiology of AMI. In the present study, we carefully explored the effects of miR-122 on myocardial hypoxia injury and its possible underlying mechanism. MATERIAL AND METHODS miR-122 expression was analyzed in H9c2 cardiomyocytes after being transfected with miR-122 mimic, ASO-miR-122, or negative control. Cell viability and apoptosis were investigated by CCK-8 assays and flow cytometry analysis, respectively...
September 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28867208/inter-adipocyte-adhesion-and-signaling-by-collagen-iv-intercellular-concentrations-in-drosophila
#18
Jianli Dai, Mengqi Ma, Zhi Feng, José C Pastor-Pareja
Sheet-forming Collagen IV is the main component of basement membranes, which are planar polymers of extracellular matrix underlying epithelia and surrounding organs in all animals. Adipocytes in both insects and mammals are mesodermal in origin and often classified as mesenchymal. However, they form true tissues where cells remain compactly associated. Neither the mechanisms providing this tissue-level organization nor its functional significance are known. Here we show that discrete Collagen IV intercellular concentrations (CIVICs), distinct from basement membranes and thicker in section, mediate inter-adipocyte adhesion in Drosophila...
August 23, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28861148/a-proteomics-based-investigation-on-the-anticancer-activity-of-alisertib-an-aurora-kinase-a-inhibitor-in-hepatocellular-carcinoma-hep3b-cells
#19
Qiaohua Zhu, Meihua Luo, Chengyu Zhou, Zhiwei Zhou, Zhixu He, Xinfa Yu, Shufeng Zhou
Targeted therapy may provide survival benefit for advanced hepatocellular carcinoma (HCC) and Aurora A kinase (AURKA) represents a feasible target in cancer treatment. The purpose of this study is to investigate the anticancer activity of alisertib (ALS) on Hep3B cells based on a proteomic study conducted with the stable-isotope labeling by amino acids in cell culture (SILAC). The proteomic response to ALS was obtained with SILAC-based proteomic study. Cell cycle distribution and apoptosis were assessed using flow cytometry and autophagy was determined using flow cytometry and confocal microscopy...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28858266/kinases-involved-in-both-autophagy-and-mitosis
#20
REVIEW
Zhiyuan Li, Xin Zhang
Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis...
August 31, 2017: International Journal of Molecular Sciences
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