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https://www.readbyqxmd.com/read/27921076/yeast-2-hybrid-data-file-showing-progranulin-interactions-in-human-fetal-brain-and-bone-marrow-libraries
#1
Irmgard Tegeder
Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#2
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27911800/an-%C3%AE-%C3%AE-hydrolase-fold-protein-in-the-biosynthesis-of-thiostrepton-exhibits-a-dual-activity-for-endopeptidyl-hydrolysis-and-epoxide-ring-opening-macrocyclization
#3
Qingfei Zheng, Shoufeng Wang, Panpan Duan, Rijing Liao, Dandan Chen, Wen Liu
Thiostrepton (TSR), an archetypal bimacrocyclic thiopeptide antibiotic that arises from complex posttranslational modifications of a genetically encoded precursor peptide, possesses a quinaldic acid (QA) moiety within the side-ring system of a thiopeptide-characteristic framework. Focusing on selective engineering of the QA moiety, i.e., by fluorination or methylation, we have recently designed and biosynthesized biologically more active TSR analogs. Using these analogs as chemical probes, we uncovered an unusual indirect mechanism of TSR-type thiopeptides, which are able to act against intracellular pathogens through host autophagy induction in addition to direct targeting of bacterial ribosome...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27901110/the-rodent-malaria-liver-stage-survives-in-the-rapamycin-induced-autophagosome-of-infected-hepa1-6-cells
#4
Chenghao Zhao, Taiping Liu, Taoli Zhou, Yong Fu, Hong Zheng, Yan Ding, Kun Zhang, Wenyue Xu
It has been reported that non-selective autophagy of infected hepatocytes could facilitate the development of malaria in the liver stage, but the fate of parasites following selective autophagy of infected hepatocytes is still not very clear. Here, we confirmed that sporozoite infection can induce a selective autophagy-like process targeting EEFs (exo-erythrocytic forms) in Hepa1-6. Rapamycin treatment greatly enhanced this process in EEFs and non-selective autophagy of infected Hepa1-6 cells and enhanced the development of the malaria liver stage in vivo...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#5
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27890807/diosmin-induced-senescence-apoptosis-and-autophagy-in-breast-cancer-cells-of-different-p53-status-and-erk-activity
#6
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Relatively low bioavailability of plant-derived nutraceuticals with anticancer properties may limit their usefulness for prevention and therapy of cancer. In the present study, we have screened for nutraceuticals (n=30) that would act at low micromolar range against phenotypically distinct breast cancer cell lines, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)), and diosmin, a citrus fruit flavonoid belonging to a flavone subclass, was selected...
November 24, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27890727/synthetic-tambjamine-analogues-induce-mitochondrial-swelling-and-lysosomal-dysfunction-leading-to-autophagy-blockade-and-necrotic-cell-death-in-lung-cancer
#7
Ananda M Rodilla, Luís Korrodi-Gregório, Elsa Hernando, Pilar Manuel-Manresa, Roberto Quesada, Ricardo Pérez-Tomás, Vanessa Soto-Cerrato
Current pharmacological treatments for lung cancer show very poor clinical outcomes, therefore, the development of novel anticancer agents with innovative mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient compared to normal cells, which favours cancer progression by promoting proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the use of ionophores to modulate intracellular pH appears as a promising new therapeutic strategy. Indeed, there is a growing body of evidence supporting ionophores as novel antitumour drugs...
November 24, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27889812/research-progress-of-hydroxychloroquine-and-autophagy-inhibitors-on-cancer
#8
REVIEW
Ting-Ting Shi, Xiao-Xu Yu, Li-Jun Yan, Hong-Tao Xiao
PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study...
November 26, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27889529/antiviral-activities-of-selected-antimalarials-against-dengue-virus-type-2-and-zika-virus
#9
Anuradha Balasubramanian, Tadahisa Teramoto, Amol A Kulkarni, Apurba K Bhattacharjee, Radhakrishnan Padmanabhan
In a previous study, twelve antimalarial compounds, amodiaquine (AQ) and derivatives, were shown to have potent anti-dengue viral (DENV) activity by using the stable DENV2 Renilla luciferase reporter replicon expressing BHK-21 cells, infectivity (plaque), and the qRT-PCR assays. In this study, we performed molecular modeling on these compounds to determine their stereo-electronic properties required for optimal antiviral activity. Based on the similarity of calculated stereo-electronic profiles, specifically the electrostatic potential profiles of the compounds, and in silico screening of related compounds from literature, we identified three additional compounds, Quinacrine (QC), Mefloquine (MQ), and GSK369796...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27884749/celecoxib-exerts-antitumor-effects-in-hl-60-acute-leukemia-cells-and-inhibits-autophagy-by-affecting-lysosome-function
#10
Ying Lu, Xiang-Fu Liu, Ting-Rong Liu, Rui-Fang Fan, Yi-Chuan Xu, Xiang-Zhong Zhang, Ling-Ling Liu
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert antitumor activity in a variety of cancer cells. The underlying mechanism involves inhibition of cell cycle progression and induction of apoptosis. Besides, celecoxib has also been found to induce autophagy in some solid tumor cells. The aim of this study was to investigate the effect of celecoxib on cell proliferation in HL-60 human acute leukemia cells and to explore the potential mechanism. HL-60 cells were exposed to various concentrations of celecoxib and cell viability was evaluated by the MTT assay...
November 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27881580/disruption-of-autophagic-degradation-with-roc-325-antagonizes-renal-cell-carcinoma-pathogenesis
#11
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Yingchun Han, Valeria Visconte, James G Phillips, Steffan T Nawrocki
PURPOSE: Although autophagy plays important roles in malignant pathogenesis and drug resistance, there are few clinical agents that disrupt this pathway and the potential therapeutic benefit of autophagy inhibition remains undetermined. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. EXPERIMENTAL DESIGN: ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC) with HCQ serving as a comparator...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880899/lc3c-contributes-to-vpu-mediated-antagonism-of-bst2-tetherin-restriction-on-hiv-1-release-through-a-non-canonical-autophagy-pathway
#12
Ursula Madjo, Olivier Leymarie, Stéphane Frémont, Aurelia Kuster, Mélanie Nehlich, Sarah Gallois-Montbrun, Katy Janvier, Clarisse Berlioz-Torrent
BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66 sequence...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880896/rnf166-determines-recruitment-of-adaptor-proteins-during-antibacterial-autophagy
#13
Robert J Heath, Gautam Goel, Leigh A Baxt, Jason S Rush, Vishnu Mohanan, Geraldine L C Paulus, Vijay Jani, Kara G Lassen, Ramnik J Xavier
Xenophagy is a form of selective autophagy that involves the targeting and elimination of intracellular pathogens through several recognition, recruitment, and ubiquitination events. E3 ubiquitin ligases control substrate selectivity in the ubiquitination cascade; however, systematic approaches to map the role of E3 ligases in antibacterial autophagy have been lacking. We screened more than 600 putative human E3 ligases, identifying E3 ligases that are required for adaptor protein recruitment and LC3-bacteria colocalization, critical steps in antibacterial autophagy...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879200/mechanism-of-cargo-directed-atg8-conjugation-during-selective-autophagy
#14
Dorotea Fracchiolla, Justyna Sawa-Makarska, Bettina Zens, Anita de Ruiter, Gabriele Zaffagnini, Andrea Brezovich, Julia Romanov, Kathrin Runggatscher, Claudine Kraft, Bojan Zagrovic, Sascha Martens
Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo receptors interact with the E3-like enzyme Atg12∼Atg5-Atg16, which stimulates Atg8 conjugation. The interaction of Atg19 with the Atg12∼Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs)...
November 23, 2016: ELife
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#15
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869116/autophagy-controls-centrosome-number-by-degrading-cep63
#16
Yuichiro Watanabe, Shinya Honda, Akimitsu Konishi, Satoko Arakawa, Michiko Murohashi, Hirofumi Yamaguchi, Satoru Torii, Minoru Tanabe, Shinji Tanaka, Eiji Warabi, Shigeomi Shimizu
Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin-proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The autophagic regulation of centrosome number is dependent on a centrosomal protein of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that are engulfed and digested by autophagy in wild-type cells, and that the upregulation of Cep63 increases centrosome number...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27868117/heteroleptic-mononuclear-compounds-of-ruthenium-ii-synthesis-structural-analyses-in-vitro-antitumor-activity-and-in-vivo-toxicity-on-zebrafish-embryos
#17
O A Lenis-Rojas, A R Fernandes, C Roma-Rodrigues, P V Baptista, F Marques, D Pérez-Fernández, J Guerra-Varela, L Sánchez, D Vázquez-García, M López Torres, A Fernández, J J Fernández
The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a-5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2'-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, (1)H and (31)P-{(1)H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(ii) complexes were determined by single crystal X-ray diffraction...
November 21, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27867387/neutrophils-discriminate-between-lipopolysaccharides-of-different-bacterial-sources-and-selectively-release-neutrophil-extracellular-traps
#18
Elmar Pieterse, Nils Rother, Cansu Yanginlar, Luuk B Hilbrands, Johan van der Vlag
The release of neutrophil extracellular traps (NETs), either during "suicidal" or "vital" NETosis, represents an important strategy of neutrophils to combat Gram-negative bacteria. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, is a reported stimulus for NET formation. Although it is widely acknowledged that the structural diversity in LPS structures can elicit heterogeneous immune responses, species- and serotype-specific differences in the capacity of LPS to trigger NET formation have not yet been investigated...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27866924/bacterial-pathogens-versus-autophagy-implications-for-therapeutic-interventions
#19
REVIEW
Jacqueline M Kimmey, Christina L Stallings
Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27866220/molecular-basis-of-mycobacterial-survival-in-macrophages
#20
REVIEW
Jane Atesoh Awuh, Trude Helen Flo
Macrophages play an essential role in the immune system by ingesting and degrading invading pathogens, initiating an inflammatory response and instructing adaptive immune cells, and resolving inflammation to restore homeostasis. More interesting is the fact that some bacteria have evolved to use macrophages as a natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of humanity's most successful pathogens and is the causal agent of tuberculosis, while NTMs cause opportunistic infections all of which are of significant public health concern...
November 19, 2016: Cellular and Molecular Life Sciences: CMLS
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