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https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#1
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29025974/lipid-based-dna-sirna-transfection-agents-disrupt-neuronal-bioenergetics-and-mitophagy
#2
Eleonora Napoli, Siming Liu, Ilaria Marsilio, Konstantinos Zarbalis, Cecilia Giulivi
A multitude of natural and artificial compounds have been recognized to modulate autophagy, providing direct or, through associated pathways, indirect entry points to activation and inhibition. While these pharmacological tools are extremely useful in the study of autophagy, their abundance also suggests the potential presence of unidentified autophagic modulators that may interfere with experimental designs if applied unknowingly. Here, we report unanticipated effects on autophagy and bioenergetics in neuronal progenitor cells (NPC) incubated with widely used lipid-based-transfection reagent lipofectamine (LF), which induced mitochondria depolarization followed by disruption of electron transport...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell-lung-cancer
#3
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024631/luteoloside-induces-g0-g1-arrest-and-pro-death-autophagy-through-the-ros-mediated-akt-mtor-p70s6k-signalling-pathway-in-human-non-small-cell-lung-cancer-cell-lines
#4
Menglu Zhou, Shuying Shen, Xin Zhao, Xingguo Gong
Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation, inducing G0/G1phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells...
October 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29024336/interplay-of-pathogenic-forms-of-human-tau-with-different-autophagic-pathways
#5
Benjamin Caballero, Yipeng Wang, Antonio Diaz, Inmaculada Tasset, Yves Robert Juste, Eva-Maria Mandelkow, Eckhard Mandelkow, Ana Maria Cuervo
Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients' brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age-related disease...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/29023824/cholangiocyte-autophagy-contributes-to-hepatic-cystogenesis-in-polycystic-liver-disease-and-represents-a-potential-therapeutic-target
#6
Anatoliy I Masyuk, Tatyana V Masyuk, Maria J Lorenzo Pisarello, Jingyi Francess Ding, Lorena Loarca, Bing Q Huang, Nicholas F LaRusso
Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed Functional Pathway Cluster Analysis (FPCA) and NextGen Sequencing (NGS), transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023512/the-ultrastructural-characteristics-of-porcine-hepatocytes-donated-after-cardiac-death-and-preserved-with-warm-machine-perfusion-preservation
#7
Hiroki Bochimoto, Naoto Matsuno, Yo Ishihara, Tatsuya Shonaka, Daisuke Koga, Yoshiki Hira, Yuji Nishikawa, Hiroyuki Furukawa, Tsuyoshi Watanabe
The effects of warm machine perfusion preservation of liver grafts donated after cardiac death on the intracellular three-dimensional ultrastructure of the organelles in hepatocytes remain unclear. Here we analyzed comparatively the ultrastructure of the endomembrane systems in porcine hepatocytes under warm ischemia and successive hypothermic and midthermic machine perfusion preservation, a type of the warm machine perfusion. Porcine liver grafts which had a warm ischemia time of 60 minutes were perfused for 4 hours with modified University of Wisconsin gluconate solution...
2017: PloS One
https://www.readbyqxmd.com/read/29022917/trehalose-protects-against-cadmium-induced-cytotoxicity-in-primary-rat-proximal-tubular-cells-via-inhibiting-apoptosis-and-restoring-autophagic-flux
#8
Xin-Yu Wang, Heng Yang, Min-Ge Wang, Du-Bao Yang, Zhen-Yong Wang, Lin Wang
Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022898/superoxide-drives-progression-of-parkin-pink1-dependent-mitophagy-following-translocation-of-parkin-to-mitochondria
#9
Bin Xiao, Xiao Deng, Grace G Y Lim, Shaoping Xie, Zhi Dong Zhou, Kah-Leong Lim, Eng-King Tan
Reactive oxygen species (ROS) and mitophagy are profoundly implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). Several studies have suggested that ROS are not involved in mitochondrial translocation of Parkin which primes mitochondria for autophagic elimination. However, whether ROS play a role in the execution of mitophagy is unknown. In the present study, we show that carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment induced both mitochondrial depolarization and generation of ROS that were needed for the mitophagy process...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022289/cloning-of-autophagy-related-micrornas
#10
Deniz Gulfem Ozturk, Muhammed Kocak, Devrim Gozuacik
Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles. Conditions resulting in cellular stress such as starvation or hypoxia might activate autophagy. Being at the crossroads of various cellular response pathways, dysregulation of autophagy might result in pathological states including cancer and neurodegenerative diseases. Autophagy has also been shown to participate in stemness. MicroRNAs were introduced as novel regulators of autophagy, and accumulating results underlined the fact that they constituted an important layer of biological control mechanism on the autophagic activity...
October 12, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29022195/high-lc3-beclin-expression-correlates-with-poor-survival-in-glioma-a-definitive-role-for-autophagy-as-evidenced-by-in-vitro-autophagic-flux
#11
Padmakrishnan Cj, Easwer Hv, Vinod Vijayakurup, Girish R Menon, Suresh Nair, Srinivas Gopala
Recent studies suggest the role of autophagy, an evolutionarily conserved catabolic process, in determining the response of gliomas to treatment either positively or negatively. The study attempts to characterize autophagy in low and high-grade glioma by investigating the autophagic flux and clinical significance of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We evaluated the expression of autophagic markers in resected specimens of low-grade glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and Western blotting...
October 11, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29021535/the-autophagy-scaffold-protein-alfy-is-critical-for-the-granulocytic-differentiation-of-aml-cells
#12
Anna M Schläfli, Pauline Isakson, E Garattini, Anne Simonsen, Mario P Tschan
Acute myeloid leukemia (AML) is a malignancy of myeloid progenitor cells that are blocked in differentiation. Acute promyelocytic leukemia (APL) is a rare form of AML, which generally presents with a t(15;17) translocation causing expression of the fusion protein PML-RARA. Pharmacological doses of all-trans retinoic acid (ATRA) induce granulocytic differentiation of APL cells leading to cure rates of >80% if combined with conventional chemotherapy. Autophagy is a lysosomal degradation pathway for the removal of cytoplasmic content and recycling of macromolecules...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021349/activation-of-autophagy-ameliorates-cardiomyopathy-in-mybpc3-targeted-knockin-mice
#13
Sonia R Singh, Antonia T L Zech, Birgit Geertz, Silke Reischmann-Düsener, Hanna Osinska, Maksymilian Prondzynski, Elisabeth Krämer, Qinghang Meng, Charles Redwood, Jolanda van der Velden, Jeffrey Robbins, Saskia Schlossarek, Lucie Carrier
BACKGROUND: Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases. MYBPC3, encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene. METHODS AND RESULTS: We evaluated autophagy in patients with HCM carrying MYBPC3 mutations and in a Mybpc3-targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice...
October 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29021346/the-hect-e3-ubiquitin-ligase-nedd4-interacts-with-and-ubiquitinates-sqstm1-for-inclusion-body-autophagy
#14
Qiong Lin, Qian Dai, Hongxia Meng, Aiqin Sun, Jing Wei, Ke Peng, Chandra Childress, Miao Chen, Genbao Shao, Wannian Yang
Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 interacts with LC3 and is required for starvation and rapamycin-induced activation of autophagy. Here we report that NEDD4 directly binds to SQSTM1 via its HECT domain and poly-ubiquitinates SQSTM1. This ubiquitination is through K63 conjugation and not involved in proteasomal degradation. Mutational analysis indicates that NEDD4 interacts with and ubiquitinates the PB1 domain of SQSTM1. Depletion of NEDD4 or overexpression of the ligase defective mutant of NEDD4 induced accumulation of aberrant enlarged SQSTM1-positive inclusion bodies that are co-localized with the endoplasmic reticulum (ER) marker CANX, suggesting that the ubiquitination functions in the SQSTM1-mediated biogenic process of inclusion body autophagosomes...
October 11, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29017169/ox-ldl-induced-microrna-155-promotes-autophagy-in-human-endothelial-cells-via-repressing-the-rheb-mtor-pathway
#15
Jinlin Lv, Lixia Yang, Ruiwei Guo, Yankun Shi, Ziwei Zhang, Jinshan Ye
BACKGROUND/AIMS: Autophagy, an evolutionary conserved biological process, is activated in cells to cope with various types of stress. MicroRNAs control several activities related to autophagy. However, the role of autophagy-related microRNAs during atherosclerosis is far from known. MicroRNA-155 was identified to be a crucial regulator of atherosclerosis. The objectives of the study were to analyze the effect of microRNA-155 on autophagic signaling and explore its mechanism in human endothelial cells under ox-LDL stress...
October 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28993461/brucella-abortus-promotes-a-fibrotic-phenotype-in-hepatic-stellate-cells-with-concomitant-autophagy-pathway-activation
#16
Paula Constanza Arriola Benitez, Ayelén Ivana Pesce Viglietti, Claudia Karina Herrmann, Vida A Dennis, Diego José Comerci, Guillermo Hernán Giambartolomei, María Victoria Delpino
The liver is frequently affected in patients with active brucellosis. The present study demonstrates that B. abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promote a profibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by up-regulation of the LC3II/LC3I ratio and beclin-1 expression as well as inhibition of p62 expression in infected cells...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28993455/ehrlichia-activation-of-wnt-pi3k-mtor-signaling-inhibits-autolysosome-generation-and-autophagic-destruction-by-the-mononuclear-phagocyte
#17
Taslima T Lina, Tian Luo, Thangam-Sudha Velayutham, Seema Das, Jere W McBride
In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium, Ehrlichia chaffeensis, resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this study, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by presence of autophagy markers such as LC3, Beclin-1 and p62...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28993153/tfeb-activation-protects-against-cardiac-proteotoxicity-via-increasing-autophagic-flux
#18
Bo Pan, Hanming Zhang, Taixing Cui, Xuejun Wang
Insufficient lysosomal removal of autophagic cargoes in cardiomyocytes has been suggested as a main cause for the impairment of the autophagic-lysosomal pathway (ALP) in many forms of heart disease including cardiac proteinopathy and may play an important pathogenic role; however, the molecular basis and the correcting strategy for the cardiac ALP insufficiency require further investigation. The present study was sought to determine whether myocardial expression and activity of TFEB, the recently identified ALP master regulator, are impaired in a cardiac proteinopathy mouse model and to determine the effect of genetic manipulation of TFEB expression on autophagy and proteotoxicity in a cardiomyocyte model of proteinopathy...
October 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28990778/benzo-a-pyrene-induces-autophagic-and-pyroptotic-death-simultaneously-in-hl-7702-human-normal-liver-cells
#19
Li Yuan, Junyi Liu, Hong Deng, Chunxia Gao
As a common polycyclic aromatic hydrocarbon compound, benzo(α)pyrene (BaP) is readily produced in processing of oil and fatty foods. It is not only a strong carcinogen, but also a substance with strong immunotoxicity and reproduction toxicity. Autophagy and pyroptosis are two types of programmed cell death. Whether or not BaP damages body tissues via autophagy or pyroptosis remains unknown. The present study investigated the effects of BaP on autophagy and pyroptosis in HL-7702 cells. The results showed that BaP induced cell death in HL-7702 cells, enhanced the intracellular levels of ROS, arrested cell cycle at the S phase...
October 9, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28990517/anesthetic-agents-and-neuronal-autophagy-what-we-know-and-what-we-don-t
#20
Lili Xu, Jianjun Shen, Patrick M McQuillan, Zhiyong Hu
Numerous experimental data have demonstrated that neonatal animal exposure to commonly used anesthetic agents may cause neuronal death resulting in cognitive impairment. The underlying mechanism(s) remain elusive. Depending on the circumstances, autophagy may produce an effect that can be either protective or deleterious. Recent evidence demonstrates that this process can reduce the development of ethanol induced neurotoxicity and, as we know, ethanol has γ-Aminobutyric acid (GABA) agonist and N-methyl-D-aspartate (NMDA) antagonist characteristics similar to commonly used volatile anesthetic agents...
October 9, 2017: Current Medicinal Chemistry
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