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https://www.readbyqxmd.com/read/29232556/mst4-phosphorylation-of-atg4b-regulates-autophagic-activity-tumorigenicity-and-radioresistance-in-glioblastoma
#1
Tianzhi Huang, Chung Kwon Kim, Angel A Alvarez, Rajendra P Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M Horbinski, Songjian Lu, Roger Stupp, John A Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29230017/systematic-analysis-of-ribophagy-in-human-cells-reveals-bystander-flux-during-selective-autophagy
#2
Heeseon An, J Wade Harper
Ribosomes are abundant cellular machines 1,2 that are regulated by assembly, supernumerary subunit turnover and nascent chain quality control mechanisms 1-5 . Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system dependent manner, a process called 'ribophagy' 6,7 . However, whether ribophagy in mammals is selective or regulated is unclear. Using Ribo-Keima flux reporters, we find that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which, unlike yeast, is largely independent of ATG8 conjugation and occurs concomitantly with other cytosolic protein autophagic flux reporters 8,9 ...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29229994/autophagy-induced-during-apoptosis-degrades-mitochondria-and-inhibits-type-i-interferon-secretion
#3
Lisa M Lindqvist, Daniel Frank, Kate McArthur, Toby A Dite, Michael Lazarou, Jonathan S Oakhill, Benjamin T Kile, David L Vaux
Cells undergoing Bax/Bak-mediated apoptosis exhibit signs of autophagy, but how it is activated and its significance is unknown. By directly activating Bax/Bak with BH3-only proteins or BH3 mimetic compounds, we demonstrate that mitochondrial damage correlated with a rapid increase in intracellular [AMP]/[ATP], phosphorylation of 5' AMP-activated protein kinase (AMPK), and activation of unc-51 like autophagy activating kinase 1 (ULK1). Consequently, autophagic flux was triggered early in the apoptotic pathway, as activation of the apoptosome and caspases were not necessary for its induction...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229567/rice-stripe-virus-interferes-with-s-acylation-of-remorin-and-induces-its-autophagic-degradation-to-facilitate-virus-infection
#4
Shuai Fu, Yi Xu, Chenyang Li, Yi Li, Jianxiang Wu, Xueping Zhou
Remorins are plant-specific membrane-associated proteins, and were proposed to play crucial roles in plant-pathogen interactions. However, little is known about pathogens' counter-response to remorin-mediated regulation. Here, we find the remorin protein (NbREM1) is down-regulated early in Rice stripe virus (RSV) infection by quantitative whole-proteome analysis. We demonstrate that the turnover of NbREM1 is regulated by the S-acylation modification and can enter the autophagy pathway for degradation. We further show that RSV can interfere with the S-acylation of NbREM1, that is required for negatively regulates RSV infection by restricting virus cell-to-cell trafficking...
December 8, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29229534/a-novel-compound-dt-010-protects-against-doxorubicin-induced-cardiotoxicity-in-zebrafish-and-h9c2-cells-by-inhibiting-reactive-oxygen-species-mediated-apoptotic-and-autophagic-pathways
#5
Fan Tang, Xinhua Zhou, Liang Wang, Luchen Shan, Chuwen Li, Hefeng Zhou, Simon Ming-Yuen Lee, Maggie Pui-Man Hoi
Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29228704/role-of-hif-1a-in-regulating-autophagic-cell-survival-during-cerebral-ischemia-reperfusion-in-rats
#6
Yongqing Guo
Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228587/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#7
Angela Ianniciello, Pierre-Yves Dumas, Claire Drullion, Amélie Guitart, Arnaud Villacreces, Yan Peytour, Jean Chevaleyre, Philippe Brunet de la Grange, Isabelle Vigon, Vanessa Desplat, Muriel Priault, Persio Dello Sbarba, Zoran Ivanovic, François-Xavier Mahon, Jean-Max Pasquet
Albeit tyrosine kinase inhibitors anti-Abl used in Chronic Myeloid Leukemia (CML) block the deregulated activity of the Bcr-Abl tyrosine kinase and induce remission in 90% of patients, they do not eradicate immature hematopoietic compartments of leukemic stem cells. To elucidate if autophagy is important for stem cell survival and/or proliferation, we used culture in low oxygen concentration (0.1% O2 for 7 days) followed back by non-restricted O2 supply (normoxic culture) to mimic stem cell proliferation and commitment...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228561/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#8
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227549/in-vitro-dissection-of-autophagy
#9
Min Zhang, Dawei Liu, Liang Ge
Autophagy is an essential cellular process for bulk degradation of cytoplasmic components through the lysosome. Underlying this process is an intricate interaction between protein factors and the cell endomembrane system, leading to a gradual maturation of the autophagic membrane. This structure sequesters a portion of the cytoplasm by the formation of a double-membrane compartment called the autophagosome. The autophagosome then delivers the cargo to the lysosome to complete degradation. The molecular mechanism accounting for the generation of the autophagic membrane is a longstanding question...
December 11, 2017: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/29225688/repurposing-drugs-in-oncology-redo-chloroquine-and-hydroxychloroquine-as-anti-cancer-agents
#10
Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis, Gauthier Bouche
Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29225212/iron-deficiency-induces-autophagy-and-activates-nrf2-signal-through-modulating-p62-sqstm
#11
Hirofumi Inoue, Nobuaki Hanawa, Shin-Ichi Katsumata, Rie Katsumata-Tsuboi, Nobuyuki Takahashi, Mariko Uehara
Iron is an essential trace metal in almost all organisms and plays an important role in the redox system. We previously reported that iron deficiency activated autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling for oxidative stress. However, regulatory mechanisms underlying the association between autophagy and Nrf2 signaling are unclear. In this study, we found that treatment of cells with an iron-specific chelator deferoxamine (DFO) increased reactive oxidative species (ROS) production by elevating the expression of p47phox and p67phox compared with that in untreated cells...
2017: Biomedical Research
https://www.readbyqxmd.com/read/29225132/ginsenoside-rh4-induces-apoptosis-and-autophagic-cell-death-through-activation-of-the-ros-jnk-p53-pathway-in-colorectal-cancer-cells
#12
Qian Wu, Jianjun Deng, Daidi Fan, Zhiguang Duan, Chenhui Zhu, Rongzhan Fu, Shanshan Wang
The use of ginsenosides in cancer therapy has been intensively investigated. The ginsenoside Rh4 (Rh4), a rare saponin obtained from Panax notoginseng, dissolves in water more readily than total saponins, making this compound easier to use in anti-cancer pharmaceutics. Here, we investigated the antiproliferative activity and mechanisms of Rh4 in colorectal cancer, both in vivo and in vitro. A colorectal cancer xenograft model showed that Rh4 significantly inhibited tumor growth with few side effects. CCK-8 assays, flow cytometric analysis, Western blotting and immunohistochemistry revealed that Rh4 effectively suppressed colorectal cancer cell proliferation via inducing G0/G1 phase arrest, caspase-dependent apoptosis and autophagic cell death but was not significantly cytotoxic to normal colon epithelial cells...
December 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29223571/noval-nitroaromatic-compound-activates-autophagy-and-apoptosis-pathways-in-hl60%C3%A2-cells
#13
Gabriele Mendes M C Perdigão, Marcela Silva Lopes, Lucas Bonfim Marques, Pedro Henrique Dias Moura Prazeres, Kamila de Sousa Gomes, Renata Barbosa de Oliveira, Mauro Cunha Xavier Pinto, Elaine Maria de Souza-Fagundes
N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a nitroaromatic bioreductible compound with cytotoxic effects in cancer cells lines. The aim of this work was investigated the molecular mechanisms involved in cell death promoted by NBCN on HL60 cells line. We observed that NBCN treatment increased intracellular ROS, reduced mitochondria membrane potential (ΔΨm). The treatment also induced morphological changes, phosphatidylserine exposure, cell cycle arrest in G2/M-phase, DNA condensation and fragmentation in HL60 cells, but did not showed cytotoxic effects on normal human peripheral blood mononuclear cells (PBMC)...
December 6, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29222055/autophagy-plays-a-protective-role-in-mn-induced-toxicity-in-pc12-cells
#14
Qian Zhou, Xiaolong Fu, Xueting Wang, Qin Wu, Yuanfu Lu, Jingshan Shi, James E Klaunig, Shaoyu Zhou
Excessive environmental or occupational exposure to manganese (Mn) is associated with increased risk of neuron degenerative disorders. Oxidative stress and mitochondrial dysfunction are the main mechanisms of Mn mediated neurotoxicity. Selective removal of damaged mitochondria by autophagy has been proposed as a protective mechanism against neuronal toxicant-induced neurotoxicity. Whether autophagic flux plays a role in Mn-induced cytotoxicity remains to be fully elucidated. The present study was designed to investigate the effect of Mn exposure on autophagy, and how modulation of autophagic flux alters the sensitivities of cells to Mn-elicited cytotoxicity...
December 6, 2017: Toxicology
https://www.readbyqxmd.com/read/29221764/regulation-of-autophagy-by-polyphenols-paving-the-road-for-treatment-of-neurodegeneration
#15
REVIEW
Seyed Fazel Nabavi, Antoni Sureda, Ahmad Reza Dehpour, Samira Shirooie, Ana Sanches Silva, Kasi Pandima Devi, Touqeer Ahmed, Nafeesa Ishaq, Rabia Hashim, Eduardo Sobarzo-Sánchez, Maria Daglia, Nady Braidy, Mariateresa Volpicella, Rosa Anna Vacca, Seyed Mohammad Nabavi
In the present paper, we will discuss on the importance of autophagy in the central nervous system, and outline the relation between autophagic pathways and the pathogenesis of neurodegenerative disorders. The potential therapeutic benefits of naturally occurring phytochemicals as pharmacological modulators of autophagy will also be addressed. Our findings provide renewed insight on the molecular modes of protection by polyphenols, which is likely to be at least in part mediated not only by their potent antioxidant and anti-inflammatory effects, but also through modulation of autophagic processes to remove the aberrant protein aggregates...
December 5, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/29219657/the-levels-of-mutant-k-ras-and-mutant-n-ras-are-rapidly-reduced-in-a-beclin1-atg5-dependent-fashion-by-the-irreversible-erbb1-2-4-inhibitor-neratinib
#16
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Cindy Sander, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29218765/deregulation-of-autophagy-in-postmortem-brains-of-machado-joseph-disease-patients
#17
Annie Sittler, Marie-Paule Muriel, Martina Marinello, Alexis Brice, Wilfred den Dunnen, Sandro Alves
Autophagy, the major pathway for protein turnover, is critical to maintain cellular homeostasis and has been implicated in neurodegenerative diseases. The aim of this research was to analyze the expression of autophagy markers in postmortem brains from Machado-Joseph disease (MJD) patients. The expression of autophagy markers in the cerebellum and the oculomotor nucleus from MJD patients and age-matched controls with no signs of neuropathology was inspected postmortem by immunohistochemistry (IHC) and Western blot...
December 8, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29216269/compensatory-role-of-neuroglobin-in-nervous-and-non-nervous-cancer-cells-in-response-to-the-nutrient-deprivation
#18
Marco Fiocchetti, Manuela Cipolletti, Maria Marino
Environmental factors or adverse growth conditions that may reduce cell function or viability are considered stress. The cell ability to sense and respond to environmental stresses determine its function and survival destiny. We recently defined Neuroglobin (NGB), a heme-protein, as a compensatory protein in the 17β-Estradiol (E2) anti-apoptotic activity and as a sensor of oxidative stress in both neurons and breast cancer cells. Here, the possibility that NGB levels could represent a pivotal regulator of integrated response of cancer cells to stress has been evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/29215735/vacuolated-pas-positive-lymphocytes-as-an-hallmark-of-pompe-disease-and-other-myopathies-related-to-impaired-autophagy
#19
Angelo Pascarella, Chiara Terracciano, Olimpia Farina, Luca Lombardi, Teresa Esposito, Filomena Napolitano, Giuseppina Franzese, Giovanni Panella, Francesco Tuccillo, Giancarlo la Marca, Sergio Bernardini, Silvia Boffo, Antonio Giordano, Mariarosa Anna Beatrice Melone, Giuseppe Di Iorio, Simone Sampaolo
Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212935/tetraspanin-cd63-bridges-autophagic-and-endosomal-processes-to-regulate-exosomal-secretion-and-intracellular-signaling-of-epstein-barr-virus-lmp1
#20
Stephanie N Hurwitz, Mujeeb R Cheerathodi, Dingani Nkosi, Sara B York, David G Meckes
The tetraspanin protein CD63 has been recently described as a key factor in extracellular vesicle (EV) production and endosomal cargo sorting. In the context of Epstein-Barr virus (EBV) infection, CD63 is required for the efficient packaging of the major viral oncoprotein latent membrane protein 1 (LMP1) into exosomes and other EV populations, and acts as a negative regulator of LMP1 intracellular signaling. Accumulating evidence has also pointed to intersections of the endosomal and autophagy pathways in maintaining cellular secretory processes, and as sites for viral assembly and replication...
December 6, 2017: Journal of Virology
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