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https://www.readbyqxmd.com/read/28423647/upregulation-of-the-lncrna-meg3-induces-autophagy-to-inhibit-tumorigenesis-and-progression-of-epithelial-ovarian-carcinoma-by-regulating-activity-of-atg3
#1
Yin-Ling Xiu, Kai-Xuan Sun, Xi Chen, Shuo Chen, Yang Zhao, Qing-Guo Guo, Zhi-Hong Zong
Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this study, we found that the expression of Meg3 was lower in epithelial ovarian carcinoma, and has potential to be considered as a biomarker for ovarian cancer. After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3, phenotypic changes and autophagy-related molecules were examined...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413178/synthesized-a%C3%AE-42-caused-intracellular-oxidative-damage-leading-to-cell-death-via-lysosome-rupture
#2
Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28390177/role-of-the-lysosomal-membrane-protein-cln3-in-the-regulation-of-cathepsin-d-activity
#3
Jaime Cárcel-Trullols, Attila D Kovács, David A Pearce
Among Neuronal Ceroid Lipofuscinoses (NCLs), which are childhood fatal neurodegenerative disorders, the juvenile onset form (JNCL) is the most common. JNCL is caused by recessive mutations in the CLN3 gene. CLN3 encodes a lysosomal/endosomal transmembrane protein but its precise function is not completely known. We have previously reported that in baby hamster kidney (BHK) cells stably expressing myc-tagged human CLN3 (myc-CLN3), hyperosmotic conditions drastically increased myc-CLN3 mRNA and protein expression...
April 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28381826/recombinant-tandem-of-pore-domains-in-a-weakly-inward-rectifying-k-channel-2-twik2-forms-active-lysosomal-channels
#4
Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G Meuth, Florian Lesage
Recombinant TWIK2 channels produce weak basal background K(+) currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365875/effects-of-dha-on-hippocampal-autophagy-and-lysosome-function-after-traumatic-brain-injury
#5
Yan Yin, Eric Li, George Sun, Hong Q Yan, Lesley M Foley, Liwia A Andrzejczuk, Insiya Y Attarwala, T Kevin Hitchens, Kirill Kiselyov, C Edward Dixon, Dandan Sun
Traumatic brain injury (TBI) triggers endoplasmic reticulum (ER) stress and impairs autophagic clearance of damaged organelles and toxic macromolecules. In this study, we investigated the effects of the post-TBI administration of docosahexaenoic acid (DHA) on improving hippocampal autophagy flux and cognitive functions of rats. TBI was induced by cortical contusion injury in Sprague-Dawley rats, which received DHA (16 mg/kg in DMSO, intraperitoneal administration) or vehicle DMSO (1 ml/kg) with an initial dose within 15 min after the injury, followed by a daily dose for 3 or 7 days...
April 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#6
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28320834/early-intracellular-trafficking-of-granulibacter-bethesdensis-in-human-macrophages
#7
Jessica Chu, Margery G Smelkinson, David W Dorward, Kol A Zarember, John I Gallin
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that bacteriostatic activity of monocyte derived macrophages (MDM) requires NOX2 and IFNγ-pretreatment. To determine if G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#8
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28287144/mir-153-regulates-amelogenesis-by-targeting-endocytotic-and-endosomal-lysosomal-pathways-novel-insight-into-the-origins-of-enamel-pathologies
#9
Kaifeng Yin, Wenting Lin, Jing Guo, Toshihiro Sugiyama, Malcolm L Snead, Joseph G Hacia, Michael L Paine
Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28278296/robust-growth-of-avirulent-phase-ii-coxiella-burnetii-in-bone-marrow-derived-murine-macrophages
#10
Diane C Cockrell, Carrie M Long, Shelly J Robertson, Jeffrey G Shannon, Heather E Miller, Lara Myers, Charles L Larson, Tregei Starr, Paul A Beare, Robert A Heinzen
Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent phase I, Coxiella burnetii. Growth restriction of phase II bacteria is thought to result from potentiated recognition of pathogen-associated molecular patterns, which leads to production of inhibitory effector molecules. Past studies have used conditioned medium from L-929 murine fibroblasts as a source of macrophage-colony stimulating factor (M-CSF) to promote differentiation of bone marrow-derived myeloid precursors into macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28264968/tim-3-is-a-marker-of-plasmacytoid-dendritic-cell-dysfunction-during-hiv-infection-and-is-associated-with-the-recruitment-of-irf7-and-p85-into-lysosomes-and-with-the-submembrane-displacement-of-tlr9
#11
Jordan Ari Schwartz, Kiera L Clayton, Shariq Mujib, Hongliang Zhang, A K M Nur-Ur Rahman, Jun Liu, Feng Yun Yue, Erika Benko, Colin Kovacs, Mario A Ostrowski
In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28254759/autophagosomes-cooperate-in-the-degradation-of-intracellular-c-terminal-fragments-of-the-amyloid-precursor-protein-via-the-mvb-lysosomal-pathway
#12
Alexis E González, Vanessa C Muñoz, Viviana A Cavieres, Hianara A Bustamante, Víctor-Hugo Cornejo, Yunan C Januário, Ibeth González, Claudio Hetz, Luis L daSilva, Alejandro Rojas-Fernández, Ronald T Hay, Gonzalo A Mardones, Patricia V Burgos
Brain regions affected by Alzheimer disease (AD) display well-recognized early neuropathologic features in the endolysosomal and autophagy systems of neurons, including enlargement of endosomal compartments, progressive accumulation of autophagic vacuoles, and lysosomal dysfunction. Although the primary causes of these disturbances are still under investigation, a growing body of evidence suggests that the amyloid precursor protein (APP) intracellular C-terminal fragment β (C99), generated by cleavage of APP by β-site APP cleaving enzyme 1 (BACE-1), is the primary cause of the endosome enlargement in AD and the earliest initiator of synaptic plasticity and long-term memory impairment...
March 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28213849/widespread-expression-of-a-membrane-tethered-version-of-the-soluble-lysosomal-enzyme-palmitoyl-protein-thioesterase-1
#13
Charles Shyng, Shannon L Macauley, Joshua T Dearborn, Mark S Sands
"Cross-correction," the transfer of soluble lysosomal enzymes between neighboring cells, forms the foundation for therapeutics of lysosomal storage disorders (LSDs). However, "cross-correction" poses a significant barrier to studying the role of specific cell types in LSD pathogenesis. By expressing the native enzyme in only one cell type, neighboring cell types are invariably corrected. In this study, we present a strategy to limit "cross-correction" of palmitoyl-protein thioesterase-1(PPT1), a lysosomal hydrolase deficient in Infantile Neuronal Ceroid Lipofuscinosis (INCL, Infantile Batten disease) to the lysosomal membrane via the C-terminus of lysosomal associated membrane protein-1 (LAMP1)...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#14
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195074/induction-of-autophagy-in-the-porcine-corpus-luteum-of-pregnancy-following-anti-androgen-treatment
#15
M Grzesiak, K Knapczyk-Stwora, M Slomczynska
Experimentally induced androgen deficiency during late pregnancy leads to decreased progesterone synthesis in the porcine corpus luteum (CL), which suggested an onset of functional luteolysis. It was shown that luteal regression in mammals involves not only apoptosis but also autophagy. Therefore, this study aimed to examine whether anti-androgen flutamide treatment during late pregnancy in pigs induces apoptosis and/or autophagy within luteal cells. Flutamide (50 mg/kg b.w.) was administered into pregnant gilts between 83 - 89 (GD90F) or 101 - 107 (GD108F) gestational days (GD)...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28139295/hypercalcemia-induces-targeted-autophagic-degradation-of-aquaporin-2-at-the-onset-of-nephrogenic-diabetes-insipidus
#16
Sookkasem Khositseth, Komgrid Charngkaew, Chatikorn Boonkrai, Poorichaya Somparn, Panapat Uawithya, Nusara Chomanee, D Michael Payne, Robert A Fenton, Trairak Pisitkun
Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased...
January 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28094782/cocaine-enhances-dc-to-t-cell-hiv-1-transmission-by-activating-dc-sign-larg-lsp1-complex-and-facilitating-infectious-synapse-formation
#17
Anil Prasad, Rutuja Kulkarni, Shuxian Jiang, Jerome E Groopman
DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated 'signalosome' complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088446/identification-and-characterization-of-cell-bound-membrane-vesicles
#18
Qisheng Tang, Xiaojun Zhang, Wendiao Zhang, Siyuan Zhao, Yong Chen
In contrast to the released/circulating membrane vesicles (extracellular vesicles), cell-bound membrane vesicles are poorly identified and characterized. In this study, cell-bound membrane vesicles on human umbilical vein endothelial cells (HUVECs) and human hepatoma HepG-2 cells were investigated. We identified that cell-bound membrane vesicles are not co-localized with the major markers for extracellular vesicles (e.g. phosphatidylserine, CD63, CD107α, CD31, and DNA fragments for the three well-known types of extracellular vesicles) and for intracellular organelles with similar sizes (e...
January 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28032328/targeting-exogenous-%C3%AE-defensin-to-the-endolysosomal-compartment-via-a-vehicle-guided-system
#19
Lorena Carvelli, Yuan Libin, Sherry Esfandnia, Yan Zhang, John F Presley, Carlos R Morales
A number of pathogens for which there are no effective treatments infect the cells via endocytosis. Once in the endosomes, the pathogens complete their life cycle by overriding normal lysosomal functions. Recently, our laboratory identified the lysosomal targeting signal of prosaposin, which is recognized by the sorting receptor "sortilin". Based on this evidence, we tested whether the antimicrobial peptide β-Defensin linked to the targeting sequence of prosaposin (βD-PSAP) could be redirected from its secretory pathway to the endolysosomal compartment...
December 29, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/28017659/the-ubiquitin-ligase-smurf1-functions-in-selective-autophagy-of-mycobacterium-tuberculosis-and-anti-tuberculous-host-defense
#20
Luis H Franco, Vidhya R Nair, Caitlyn R Scharn, Ramnik J Xavier, Jose R Torrealba, Michael U Shiloh, Beth Levine
During antibacterial autophagy, ubiquitination of intracellular bacteria recruits proteins that mediate bacterial delivery to the lysosome for degradation. Smurf1 is an E3 ubiquitin ligase whose role in selective bacterial autophagy is unknown. We show that Smurf1 facilitates selective autophagy of the human pathogen Mycobacterium tuberculosis (Mtb). Smurf1(-/-) macrophages are defective in recruiting polyubiquitin, the proteasome, the ubiquitin-binding autophagy adaptor NBR1, the autophagy protein LC3, and the lysosomal marker LAMP1 to Mtb-associated structures and are more permissive for Mtb growth...
January 11, 2017: Cell Host & Microbe
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