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https://www.readbyqxmd.com/read/28213849/widespread-expression-of-a-membrane-tethered-version-of-the-soluble-lysosomal-enzyme-palmitoyl-protein-thioesterase-1
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27832934/abcb1-2677g-t-a-variant-enhances-chemosensitivity-to-anti-cancer-agents-acting-on-microtubule-dynamics-through-lamp1-inhibition
#14
Woo Sun Kwon, Sun Young Rha, Hei-Cheul Jeung, Joong Bae Ahn, Jae-Joon Jung, Dong Hyuk Ki, Tae Soo Kim, Hyun Cheol Chung
Overexpression of ABCB1 associated with single nucleotide variants in cancers was reported to encode a protein responsible for drug resistance. We studied chemosensitivity-related genes associated with ABCB1 2677G>T/A variant. The associated genes were identified based on the results of the significance analysis of microarray, and then prediction accuracy was evaluated using the prediction analysis of microarray. Functional assay of the selected gene was performed by using siRNA and drug accumulation study...
January 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27788920/lamp1-expression-is-associated-with-malignant-behaviours-and-predicts-unfavourable-prognosis-in-laryngeal-squamous-cell-carcinoma
#15
Meiping Lu, Huijun Zhu, Xudong Wang, Dawei Zhang, Lin Xiong, Jin Zhu, Yuan Mao, Jianfeng Qiang
Lysosome-associated membrane protein-1 (LAMP1) has been suggested to play complicated roles in cancer development and metastasis. The aim of this study was to explore the expression of LAMP1 in laryngeal squamous cell carcinoma (LSCC) and investigate the relationship between LAMP1 expression and clinicopathological characteristics in LSCC patients. One-step quantitative reverse transcription PCR (qPCR) tests (20 fresh LSCC and non-cancerous tissue samples) and immunohistochemistry (IHC) analyses (137 paraffin-embedded LSCC and non-cancerous tissue samples) were performed to evaluate the LAMP1 expression in both mRNA and protein levels...
December 2016: Pathology
https://www.readbyqxmd.com/read/27780934/patient-fibroblasts-derived-induced-neurons-demonstrate-autonomous-neuronal-defects-in-adult-onset-krabbe-disease
#16
Su Min Lim, Byung-Ok Choi, Seong-Il Oh, Won Jun Choi, Ki-Wook Oh, Minyeop Nahm, Yuanchao Xue, Jae Hyeok Choi, Ji Young Choi, Young-Eun Kim, Ki Wha Chung, Xiang-Dong Fu, Chang-Seok Ki, Seung Hyun Kim
Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD...
15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27773683/autophagy-lysosome-dysfunction-is-involved-in-a%C3%AE-deposition-in-stz-induced-diabetic-rats
#17
Lou-Yan Ma, Ya-Li Lv, Kang Huo, Jie Liu, Su-Hang Shang, Yu-Lang Fei, Yan-Bo Li, Bei-Yu Zhao, Meng Wei, Yong-Ning Deng, Qiu-Min Qu
β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0...
October 20, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27771328/holocrine-secretion-of-sebum-is-a-unique-dnase2-dependent-mode-of-programmed-cell-death
#18
Heinz Fischer, Judith Fumicz, Heidemarie Rossiter, Markus Napirei, Maria Buchberger, Erwin Tschachler, Leopold Eckhart
Sebaceous glands produce sebum via holocrine secretion, a largely uncharacterized mode of programmed cell death that contributes to the homeostasis and barrier function of the skin. To determine the mechanism of DNA degradation during sebocyte cell death, we have inactivated candidate DNA-degrading enzymes by targeted gene deletions in mice. DNase1 and DNase1-like 2 were dispensable for nuclear DNA degradation in sebocytes. By contrast, epithelial cell-specific deletion of lysosomal DNase2 blocked DNA degradation in these cells...
October 19, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27742708/a-new-molecular-link-between-defective-autophagy-and-erythroid-abnormalities-in-chorea-acanthocytosis
#19
Francesca Lupo, Elena Tibaldi, Alessandro Matte, Alok K Sharma, Anna Maria Brunati, Seth L Alper, Carlo Zancanaro, Donatella Benati, Angela Siciliano, Mariarita Bertoldi, Francesca Zonta, Alexander Storch, Ruth H Walker, Adrian Danek, Benedikt Bader, Andreas Hermann, Lucia De Franceschi
Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1 and Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27727322/identification-of-putative-receptors-for-the-novel-adipokine-ctrp3-using-ligand-receptor-capture-technology
#20
Ying Li, Tammy Ozment, Gary L Wright, Jonathan M Peterson
METHODS: We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a control ligand was performed on the H4IIE rat hepatoma cell line. RESULTS: Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry analysis (FACS) demonstrated successful oxidation and crosslinking of CTRP3-TriCEPS and Insulin-TriCEPS complexes to cell surface glycans...
2016: PloS One
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