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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27966067/cathepsin-b-improves-%C3%A3-amyloidosis-and-learning-and-memory-in-models-of-alzheimer-s-disease
#16
Christine M Embury, Bhagyalaxmi Dyavarshetty, Yaman Lu, Jayme L Wiederin, Pawel Ciborowski, Howard E Gendelman, Tomomi Kiyota
Amyloid-ß (Aß) precursor protein (APP) metabolism engages neuronal endolysosomal pathways for Aß processing and secretion. In Alzheimer's disease (AD), dysregulation of APP leads to excess Aß and neuronal dysfunction; suggesting that neuronal APP/Aß trafficking can be targeted for therapeutic gain. Cathepsin B (CatB) is a lysosomal cysteine protease that can lower Aß levels. However, whether CatB-modulation of Aß improves learning and memory function deficits in AD is not known. To this end, progenitor neurons were infected with recombinant adenovirus expressing CatB and recovered cell lysates subjected to proteomic analyses...
December 13, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/27925192/pathogenic-role-of-associated-adherent-invasive-escherichia-coli-in-crohn-s-disease
#17
Giuseppe Mazzarella, Angelica Perna, Angela Marano, Angela Lucariello, Vera Rotondi Aufiero, Raffaele Melina, Germano Guerra, Fabio Silvio Taccone, Gaetano Iaquinto, Antonio De Luca
Several lines of evidence suggest that adherent-invasive E. coli (AIEC) strains play an important role in Crohn's disease (CD). The objective of this study was to investigate the pathogenic role of two AIEC strains, LF82 and O83:H1, in CD patients. Organ cultures of colonic biopsies from patients were set up to assess the effects of LF82 and O83:H1 on the expression of CEACAM6, LAMP1, HLA-DR, ICAM1 by immunohistochemistry and of IL-8, IFNΓ and TNF-α genes by RT-PCR. Moreover, on Caco2 cells we analyzed the cell cycle, the expression of MGMT and DNMT1 genes and DNA damage induced by LF82 and O83:H1, by FACS, RT-PCR and DAPI staining, respectively...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27923570/recombinant-dna-vaccine-of-hantavirus-gn-and-lamp1-induced-long-term-immune-protection-in-mice
#18
Dong-Bo Jiang, Li-Juan Sun, Lin-Feng Cheng, Jin-Peng Zhang, Shao-Bo Xiao, Yuan-Jie Sun, Shu-Ya Yang, Jing Wang, Fang-Lin Zhang, Kun Yang
BACKGROUND: Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations. METHODS & RESULTS: Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27899443/rab43-facilitates-cross-presentation-of-cell-associated-antigens-by-cd8%C3%AE-dendritic-cells
#19
Nicole M Kretzer, Derek J Theisen, Roxane Tussiwand, Carlos G Briseño, Gary E Grajales-Reyes, Xiaodi Wu, Vivek Durai, Jörn Albring, Prachi Bagadia, Theresa L Murphy, Kenneth M Murphy
In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α(+) and CD103(+) compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1(-) cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen...
December 12, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27875583/k63-linked-ubiquitination-targets-toxoplasma-gondii-for-endo-lysosomal-destruction-in-ifn%C3%AE-stimulated-human-cells
#20
Barbara Clough, Joseph D Wright, Pedro M Pereira, Elizabeth M Hirst, Ashleigh C Johnston, Ricardo Henriques, Eva-Maria Frickel
Toxoplasma gondii is the most common protozoan parasitic infection in man. Gamma interferon (IFNγ) activates haematopoietic and non-haematopoietic cells to kill the parasite and mediate host resistance. IFNγ-driven host resistance pathways and parasitic virulence factors are well described in mice, but a detailed understanding of pathways that kill Toxoplasma in human cells is lacking. Here we show, that contrary to the widely held belief that the Toxoplasma vacuole is non-fusogenic, in an immune-stimulated environment, the vacuole of type II Toxoplasma in human cells is able to fuse with the host endo-lysosomal machinery leading to parasite death by acidification...
November 2016: PLoS Pathogens
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