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https://www.readbyqxmd.com/read/29675630/saikosaponin-d-inhibits-proliferation-by-up-regulating-autophagy-via-the-camkk%C3%AE-ampk-mtor-pathway-in-adpkd-cells
#1
Weiwei Shi, Dechao Xu, Junhui Gu, Cheng Xue, Bo Yang, Lili Fu, Shuwei Song, Dongmei Liu, Wei Zhou, Jiayi Lv, Ke Sun, Meihan Chen, Changlin Mei
Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy...
April 19, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29675372/autophagy-activation-and-the-mechanism-of-retinal-microvascular-endothelial-cells-in-hypoxia
#2
Rong Li, Li-Zhao Wang, Jun-Hui Du, Lei Zhao, Yang Yao
AIM: To explore the state of autophagy and related mechanisms in the murine retinal microvascular endothelial cells (RMECs) under hypoxia stimulation. METHODS: The murine RMECs were primarily cultured and randomly divided into three groups: hypoxia group (cultured in 1% O2 environment), hypoxia+autophagy inhibition group [pretreated with 5 mmol/L 3-methyladenine (3-MA) for 4h followed by incubation in 1% O2 ] and control group (cultured under normoxic condition)...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29673078/crispr-cas9-mediated-gfp-knock-in-at-the-map1lc3b-locus-in-293ft-cells-is-better-for-bona-fide-monitoring-cellular-autophagy
#3
Zhiqiang Wu, Jinlin Zhao, Minghan Qiu, Zeyun Mi, Maobin Meng, Yu Guo, Hui Wang, Zhiyong Yuan
Accurately identifying and quantifying cellular autophagy is very important as the significance of autophagy in physiological and pathological processes becomes increasingly evident. Ectopically expressed fluorescent-tagged microtubule-associated protein light chain 3B (MAP1LC3B, LC3) is the most widely used reporter for monitoring autophagy activity thus far. However, this approach ignored the influence of constitutively overexpressed LC3 on autophagy itself and autophagy-related processes and its accuracy in indicating autophagy is questionable...
April 19, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29670377/crocin-induces-autophagic-apoptosis-in-hepatocellular-carcinoma-by-inhibiting-akt-mtor-activity
#4
Chong Yao, Bing-Bing Liu, Xiao-Dong Qian, Li-Qin Li, Heng-Bin Cao, Qiao-Sheng Guo, Gui-Fen Zhou
Background: Autophagy induction is a common mechanism for antitumor chemicals in induction of cancer cell death. However, the role of autophagy in crocin-induced apoptosis is barely studied in hepatocellular carcinoma (HCC). Materials and methods: The influence of crocin on growth, apoptosis, and autophagy and its mutual relations were analyzed by Cell Counting Kit-8 assay, flow cytometer, EGFP-LC3 puncta analysis, and Western blot in HCC cells. The activities of Akt/mTOR axis and its roles in autophagy regulation were also detected by Western blot in HCC cells treated with crocin...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29670359/d-limonene-exhibits-antitumor-activity-by-inducing-autophagy-and-apoptosis-in-lung-cancer
#5
Xiao Yu, Hongyan Lin, Yu Wang, Wenwen Lv, Shuo Zhang, Ying Qian, Xiaobei Deng, Nannan Feng, Herbert Yu, Biyun Qian
Purpose: d-limonene is a plant extract with widespread application, and it has been recently reported to have antiproliferative and proapoptotic effects on cancer cells. However, the mechanisms by which d-limonene achieves these effects, especially in lung cancer, are not entirely clear. Therefore, the goal of this study was to examine the effects of d-limonene on lung cancer and explore its mechanisms of action. Methods: We examined the therapeutic effects of d-limonene on lung cancer cells and in a xenograft animal model by characterizing its effects on the pathways of apoptosis and autophagy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29667627/propofol-inhibits-hela-cells-by-impairing-autophagic-flux-via-amp-activated-protein-kinase-ampk-activation-and-endoplasmic-reticulum-stress-regulated-by-calcium
#6
Xi Chen, Kai Li, Guoqing Zhao
BACKGROUND Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. MATERIAL AND METHODS We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#7
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29661847/the-ajuba-lim-protein-wtip-regulates-actomyosin-contractility-during-vertebrate-neural-tube-closure
#8
Chih-Wen Chu, Bo Xiang, Olga Ossipova, Andriani Ioannou, Sergei Y Sokol
Ajuba LIM proteins are implicated in the assembly of cell junctions and have been reported to antagonize Hippo signaling in response to cytoskeletal tension. To assess a role of these proteins in actomyosin contractility, we examined the localization and function of Wtip, a member of the Ajuba family, in Xenopus early embryos. Targeted in vivo depletion of Wtip inhibited apical constriction in neuroepithelial cells and elicited neural tube defects. Fluorescent protein-tagged Wtip showed predominant punctate localization along the cell junctions in the epidermis and a linear junctional pattern in the neuroectoderm...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29660306/ablation-of-toll-like-receptor-4-attenuates-aging-induced-myocardial-remodeling-and-contractile-dysfunction-through-ncori-hdac1-mediated-regulation-of-autophagy
#9
Shuyi Wang, Wei Ge, Carrie Harns, Xianzhong Meng, Yingmei Zhang, Jun Ren
Aging is usually accompanied with overt structural and functional changes as well as suppressed autophagy in the heart although the precise regulatory mechanisms are somewhat unknown. Here we evaluated the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in cardiac aging and the underlying mechanism with a focus on autophagy. Cardiac geometry and function were monitored in young or old wild-type (WT) and TLR4 knockout (TLR4-/- ) mice using echocardiography, IonOptix® edge-detection and fura-2 techniques...
April 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29649662/autophagy-attenuates-copper-induced-mitochondrial-dysfunction-by-regulating-oxidative-stress-in-chicken-hepatocytes
#10
Fan Yang, Jianzhao Liao, Ruonan Pei, Wenlan Yu, Qingyue Han, Ying Li, Jianying Guo, Lianmei Hu, Jiaqiang Pan, Zhaoxin Tang
Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO4 ) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO4 and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h...
March 29, 2018: Chemosphere
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#11
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29643768/mirna-431-prevents-amyloid-%C3%AE-induced-synapse-loss-in-neuronal-cell-culture-model-of-alzheimer-s-disease-by-silencing-kremen1
#12
Sean P Ross, Kelly E Baker, Amanda Fisher, Lee Hoff, Elena S Pak, Alexander K Murashov
Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway. Here, we show that silencing Krm1 with miR-431 prevents amyloid-β-mediated synapse loss in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29643241/truncated-cpsf6-forms-higher-order-complexes-that-bind-and-disrupt-hiv-1-capsid
#13
Jiying Ning, Zhou Zhong, Douglas K Fischer, Gemma Harris, Simon C Watkins, Zandrea Ambrose, Peijun Zhang
Cleavage and polyadenylation specificity factor 6 (CPSF6) is a human protein that binds HIV-1 capsid and mediates nuclear transport and integration targeting of HIV-1 pre-integration complexes. Truncation of the protein at its C-terminal nuclear-targeting arginine/serine-rich (RS-) domain produces a protein, CPSF6-358, that potently inhibits HIV-1 infection by targeting the capsid and inhibiting nuclear entry. To understand the molecular mechanism behind this restriction, the interaction between CPSF6-358 and HIV-1 capsid was characterized using in vitro and in vivo assays...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29628370/the-er-contact-proteins-vapa-b-interact-with-multiple-autophagy-proteins-to-modulate-autophagosome-biogenesis
#14
Yan G Zhao, Nan Liu, Guangyan Miao, Yong Chen, Hongyu Zhao, Hong Zhang
The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation...
March 31, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29627295/deficiency-of-aldose-reductase-exacerbates-early-pressure-overload-induced-cardiac-dysfunction-and-autophagy-in-mice
#15
Shahid P Baba, Deqing Zhang, Mahavir Singh, Sujith Dassanayaka, Zhengzhi Xie, Ganapathy Jagatheesan, Jingjing Zhao, Virginia K Schmidtke, Kenneth R Brittian, Michael L Merchant, Daniel J Conklin, Steven P Jones, Aruni Bhatnagar
Pathological cardiac hypertrophy is associated with the accumulation of lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) and acrolein in the heart. These aldehydes are metabolized via several pathways, of which aldose reductase (AR) represents a broad-specificity route for their elimination. We tested the hypothesis that by preventing aldehyde removal, AR deficiency accentuates the pathological effects of transverse aortic constriction (TAC). We found that the levels of AR in the heart were increased in mice subjected to TAC for 2 weeks...
April 5, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29624167/proteasome-storage-granules-protect-proteasomes-from-autophagic-degradation-upon-carbon-starvation
#16
Richard Scott Marshall, Richard David Vierstra
26S proteasome abundance is tightly regulated at multiple levels, including the elimination of excess or inactive particles by autophagy. In yeast, this proteaphagy occurs upon nitrogen starvation but not carbon starvation, which instead stimulates the rapid sequestration of proteasomes into cytoplasmic puncta termed proteasome storage granules (PSGs). Here, we show that PSGs help protect proteasomes from autophagic degradation. Both the core protease and regulatory particle sub-complexes are sequestered separately into PSGs via pathways dependent on the accessory proteins Blm10 and Spg5, respectively...
April 6, 2018: ELife
https://www.readbyqxmd.com/read/29615870/atp-and-odor-mixture-activate-trpm5-expressing-microvillous-cells-and-potentially-induce-acetylcholine-release-to-enhance-supporting-cell-endocytosis-in-mouse-main-olfactory-epithelium
#17
Ziying Fu, Tatsuya Ogura, Wangmei Luo, Weihong Lin
The main olfactory epithelium (MOE) functions to detect odor molecules, provide an epithelial surface barrier, and remove xenobiotics from inhaled air. Mechanisms coordinating the activities of different cell types within the MOE to maintain these functions are poorly understood. Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential channel M5 (TRPM5) are cholinergic and chemoresponsive and that they play an important role in maintaining odor responses and olfactory-guided behavior under challenging chemical environment...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29610350/myosin-iia-interacts-with-the-spectrin-actin-membrane-skeleton-to-control-red-blood-cell-membrane-curvature-and-deformability
#18
Alyson S Smith, Roberta B Nowak, Sitong Zhou, Michael Giannetto, David S Gokhin, Julien Papoin, Ionita C Ghiran, Lionel Blanc, Jiandi Wan, Velia M Fowler
The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes, but a function for NMII contractility in the 2D spectrin-F-actin network of RBCs has not been tested. Here, we show that RBCs contain membrane skeleton-associated NMIIA puncta, identified as bipolar filaments by superresolution fluorescence microscopy...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29606629/trans-fats-inhibit-autophagy-induced-by-saturated-fatty-acids
#19
Allan Sauvat, Guo Chen, Kevin Müller, Mingming Tong, Fanny Aprahamian, Sylvère Durand, Giulia Cerrato, Lucillia Bezu, Marion Leduc, Joakim Franz, Patrick Rockenfeller, Junichi Sadoshima, Frank Madeo, Oliver Kepp, Guido Kroemer
Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response...
March 27, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29602807/insight-from-the-maximal-activation-of-the-signal-transduction-excitable-network-in-dictyostelium-discoideum
#20
Marc Edwards, Huaqing Cai, Bedri Abubaker-Sharif, Yu Long, Thomas J Lampert, Peter N Devreotes
Cell migration requires the coordination of an excitable signal transduction network involving Ras and PI3K pathways with cytoskeletal activity. We show that expressing activated Ras GTPase-family proteins in cells lacking PTEN or other mutations which increase cellular protrusiveness transforms cells into a persistently activated state. Leading- and trailing-edge markers were found exclusively at the cell perimeter and the cytosol, respectively, of the dramatically flattened cells. In addition, the lifetimes of dynamic actin puncta were increased where they overlapped with actin waves, suggesting a mechanism for the coupling between these two networks...
March 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
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