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Selective autophagy

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https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#1
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223514/selective-autophagy-limits-cauliflower-mosaic-virus-infection-by-nbr1-mediated-targeting-of-viral-capsid-protein-and-particles
#2
Anders Hafrén, Jean-Luc Macia, Andrew J Love, Joel J Milner, Martin Drucker, Daniel Hofius
Autophagy plays a paramount role in mammalian antiviral immunity including direct targeting of viruses and their individual components, and many viruses have evolved measures to antagonize or even exploit autophagy mechanisms for the benefit of infection. In plants, however, the functions of autophagy in host immunity and viral pathogenesis are poorly understood. In this study, we have identified both anti- and proviral roles of autophagy in the compatible interaction of cauliflower mosaic virus (CaMV), a double-stranded DNA pararetrovirus, with the model plant Arabidopsis thaliana We show that the autophagy cargo receptor NEIGHBOR OF BRCA1 (NBR1) targets nonassembled and virus particle-forming capsid proteins to mediate their autophagy-dependent degradation, thereby restricting the establishment of CaMV infection...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223193/spinosad-induces-autophagy-of-spodoptera-frugiperda-sf9-cells-and-the-activation-of-ampk-mtor-signaling-pathway
#3
Mingjun Yang, Youwu Hao, Jufang Gao, Yang Zhang, Wenping Xu, Liming Tao
Spinosad, a high-selectivity neural toxin, has been widely used in agricultural production. However, the mode of action of spinosad on insect non-neural cells is not yet clear and hence requires further investigation. Therefore, to reveal the cytotoxic mechanisms of spinosad, we investigated whether and how it can induce autophagic cell death. After treating Sf9 cells with spinosad, the resulting autophagosome was observed by transmission electron microscopy and monodansylcadaverine staining. Interestingly, spinosad induced the accumulation of Beclin-1, degradation of p62, and intensification of LC3-B formation and translocation and thus autophagy, whereas, 3-MA treatment reverted the phenotype...
February 18, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28214847/contribution-of-p62-to-phenotype-transition-of-coronary-arterial-myocytes-with-defective-autophagy
#4
Junxiang Bao, Guangbi Li, Xinxu Yuan, Erich Gulbins, Pin-Lan Li
BACKGROUND: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. METHODS: Protein expression was measured by western blot analysis and immunofluorescent staining...
3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28209994/reversal-of-the-apoptotic-resistance-of-non-small-cell-lung-carcinoma-towards-trail-by-natural-product-toosendanin
#5
Xin Li, Ming You, Yong-Jian Liu, Lin Ma, Pei-Pei Jin, Ri Zhou, Zhao-Xin Zhang, Baojin Hua, Xiao-Jun Ji, Xiao-Ying Cheng, Fangzhou Yin, Yan Chen, Wu Yin
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#6
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28199887/killing-colon-cancer-cells-through-pcd-pathways-by-a-novel-hyaluronic-acid-modified-shell-core-nanoparticle-loaded-with-rip3-in-combination-with-chloroquine
#7
Xueyan Hou, Chengli Yang, Lijing Zhang, Tingting Hu, Dan Sun, Hua Cao, Fan Yang, Gang Guo, Changyang Gong, Xiaoning Zhang, Aiping Tong, Rui Li, Yu Zheng
Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding non-apoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy...
January 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28196025/autophagy-induced-by-cx-4945-a-casein-kinase-2-inhibitor-enhances-apoptosis-in-pancreatic-cancer-cell-lines
#8
Dae Wook Hwang, Kwang Sup So, Song Cheol Kim, Kwang-Min Park, Young-Joo Lee, Sun-Whe Kim, Chang-Min Choi, Jin Kyung Rho, Yun Jung Choi, Jae Cheol Lee
OBJECTIVES: Pancreatic cancer is the most lethal malignancy with only a few effective chemotherapeutic drugs. Because the inhibition of casein kinase 2 (CK2) has been reported as a novel therapeutic strategy for many cancers, we investigated the effects of CK2 inhibitors in pancreatic cancer cell lines. METHODS: The BxPC3, 8902, Mia PaCa-2 human pancreatic cancer cell lines, and CX-4945, a novel CK2 inhibitor, were used. Autophagy was analyzed by acridine orange staining, fluorescence microscope detection of punctuate patterns of GFP-tagged LC3 and immunoblotting for LC3...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28195128/a-ligand-directed-divergent-catalytic-approach-to-establish-structural-and-functional-scaffold-diversity
#9
Yen-Chun Lee, Sumersing Patil, Christopher Golz, Carsten Strohmann, Slava Ziegler, Kamal Kumar, Herbert Waldmann
The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28192531/multi-layered-control-of-galectin-8-mediated-autophagy-during-adenovirus-cell-entry-through-a-conserved-ppxy-motif-in-the-viral-capsid
#10
Charlotte Montespan, Shauna A Marvin, Sisley Austin, Andrew M Burrage, Benoit Roger, Fabienne Rayne, Muriel Faure, Edward M Campell, Carola Schneider, Rudolph Reimer, Kay Grünewald, Christopher M Wiethoff, Harald Wodrich
Cells employ active measures to restrict infection by pathogens, even prior to responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture to sequester and deliver membrane fragments and their pathogen contents for lysosomal degradation. Adenoviruses, which breach the endosome upon entry, escape this fate by penetrating into the cytosol prior to autophagosome sequestration of the ruptured endosome. We show that virus induced membrane damage is recognized through Galectin-8 and sequesters the autophagy receptors NDP52 and p62...
February 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28191006/capability-of-neutrophils-to-form-nets-is-not-directly-influenced-by-a-cma-targeting-peptide
#11
Christian Maueröder, Nicolas Schall, Frédéric Meyer, Aparna Mahajan, Benjamin Garnier, Jonas Hahn, Deborah Kienhöfer, Markus H Hoffmann, Sylviane Muller
During inflammatory reaction, neutrophils exhibit numerous cellular and immunological functions, notably the formation of neutrophil extracellular traps (NETs) and autophagy. NETs are composed of decondensed chromatin fibers coated with various antimicrobial molecules derived from neutrophil granules. NETs participate in antimicrobial defense and can also display detrimental roles and notably trigger some of the immune features of systemic lupus erythematosus (SLE) and other autoimmune diseases. Autophagy is a complex and finely regulated mechanism involved in the cell survival/death balance that may be connected to NET formation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186123/a-novel-ecg-analog-4-s-2-4-6-trimethylthiobenzyl-epigallocatechin-gallate-selectively-induces-apoptosis-of-b16-f10-melanoma-via-activation-of-autophagy-and-ros
#12
Jing Xie, Ju-Ping Yun, Ya-Nan Yang, Fang Hua, Xiao-Wei Zhang, Heng Lin, Xiao-Xi Lv, Ke Li, Pei-Cheng Zhang, Zhuo-Wei Hu
Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178760/histone-deacetylase-7-silencing-induces-apoptosis-and-autophagy-in-salivary-mucoepidermoid-carcinoma-cells
#13
Mee-Young Ahn, Jung-Hoon Yoon
BACKGROUND: The overexpression of histone deacetylases (HDACs) has been observed in many cancers and inhibition of specific HDACs has emerged as a new target for cancer therapy. We found that HDAC7 expression was selectively reduced by HDAC inhibitor apicidin in salivary mucoepidermoid carcinoma (MEC) cells. Here, we show that HDAC7 suppression has a potent anti-tumor effect in MEC cells. METHODS: HDAC7 was knocked down using HDAC7 siRNAs and cell proliferation was quantified...
February 8, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28169082/autophagy-receptors-and-neurodegenerative-diseases
#14
REVIEW
Zhiqiang Deng, Kerry Purtell, Veronik Lachance, Mitchell S Wold, Shi Chen, Zhenyu Yue
Previously thought of as a nonselective digestion process, autophagy is now known to specifically degrade aggregated proteins and damaged cellular organelles through the action of autophagy receptors, which provides cellular quality control and maintains homeostasis. Autophagy receptors recognize and recruit specific cargoes to the autophagosome-lysosome pathway for degradation in ubiquitin-dependent and -independent manners, and their functions (in selective autophagy) are regulated by protein modifications, for example, phosphorylation and ubiquitination...
February 3, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28168426/mitochondrial-metabolism-regulates-microtubule-acetylome-and-autophagy-trough-sirtuin-2-impact-for-parkinson-s-disease
#15
Ana R Esteves, Daniela M Arduíno, Diana F Silva, Sofia D Viana, Frederico C Pereira, Sandra M Cardoso
Alterations in microtubule-dependent transport, mitochondrial dysfunction, and autophagic pathology are involved in neurodegeneration observed in sporadic Parkinson's disease. However, the mechanistic link connecting these events remains elusive. We observed that NAD(+) metabolism is altered in sporadic Parkinson's disease patient-derived cells, which contributes to Sirtuin-2 activation and subsequent decrease in acetylated-α-tubulin levels. Pharmacological inhibition of sirtuin-2 deacetylase activity selectively enhanced α-tubulin acetylation and facilitated the trafficking and clearance of misfolded proteins...
February 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28166196/the-ptprot-tyrosine-phosphatase-functions-as-an-obligate-haploinsufficient-tumor-suppressor-in-vivo-in-b-cell-chronic-lymphocytic-leukemia
#16
J Wakim, E Arman, S Becker-Herman, M P Kramer, E Bakos, I Shachar, A Elson
The tyrosine phosphatase PTPROt is a suggested tumor suppressor (TS) in B-cell chronic lymphocytic leukemia (CLL), and its expression is reduced in this disease. In order to examine how reduced PTPROt expression affects CLL in vivo we induced CLL in PTPROt-targeted mice. Unexpectedly, loss of both Ptprot alleles delayed disease detection and progression and lengthened survival relative to mice carrying two intact alleles, indicating that PTPROt fulfills a novel tumor-promoting role in CLL. Tumor cells from mice lacking PTPROt exhibited reduced B-cell receptor (BCR)-induced signaling, as well as increased apoptosis and autophagy...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28165849/autophagosome-formation-and-cargo-sequestration-in-the-absence-of-lc3-gabaraps
#17
Benjamin Scott Padman, Thanh Ngoc Nguyen, Michael Lazarou
It has been widely assumed that Atg8 family LC3/GABARAP proteins are essential for the formation of autophagosomes during macroautophagy/autophagy, and the sequestration of cargo during selective autophagy. However, there is little direct evidence on the functional contribution of these proteins to autophagosome biogenesis in mammalian cells. To dissect the functions of LC3/GABARAPs during starvation-induced autophagy and PINK1-PARK2/Parkin-dependent mitophagy, we utilized CRISPR/Cas9 gene editing to generate knockouts of the LC3 and GABARAP subfamilies, and all 6 Atg8 family proteins in HeLa cells...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28159418/the-role-of-p62-sqstm1-in-sporadic-inclusion-body-myositis
#18
Satoshi Nakano, Mitsuaki Oki, Hirofumi Kusaka
We examined selective autophagy against ubiquitinated protein aggregates in sporadic inclusion body myositis (s-IBM) patients. The form of autophagy requires phosphorylation of serine 403 in p62/SQSTM1 to bind to Lys63-linked ubiquitin and the binding of the p62-ubiquitinated protein conjugates to LC3. In muscle biopsy specimens from 16 s-IBM patients, we compared the distribution of p62 (aa120-440) with 1) Ser403-phosphorylated p62 (S403-pp62), 2) Lys63-linked ubiquitin and 3) LC3 in double-colour immunofluorescence microscopy...
December 29, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28154131/a-pathway-of-targeted-autophagy-is-induced-by-dna-damage-in-budding-yeast
#19
Vinay V Eapen, David P Waterman, Amélie Bernard, Nathan Schiffmann, Enrich Sayas, Roarke Kamber, Brenda Lemos, Gonen Memisoglu, Jessie Ang, Allison Mazella, Silvia G Chuartzman, Robbie J Loewith, Maya Schuldiner, Vladimir Denic, Daniel J Klionsky, James E Haber
Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins...
February 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28153737/autophagy-an-overview-and-its-roles-in-cancer-and-obesity
#20
REVIEW
Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Ziyu Jiang, Liang Feng, Jie Song, Xiaobin Jia, Baoan Chen
Autophagy is a normal physiological process necessary for cellular homeostasis to maintain adequate levels of cellular components. It is essential to stabilize the source of energy during development and nutritional stress and plays the dual role of survival or cell killing in various diseases including cancer. The selectivity of the response to removal of selected organelles may vary according to the each type. Macroautophagy forms a double-membraned autophagosome around the organelle destined for processing...
January 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
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