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https://www.readbyqxmd.com/read/29907658/degradation-of-dendritic-cargos-requires-rab7-dependent-transport-to-somatic-lysosomes
#1
Chan Choo Yap, Laura Digilio, Lloyd P McMahon, A Denise R Garcia, Bettina Winckler
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D-positive lysosomes decreases steeply past the proximal segment...
June 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29896527/data-on-autophagy-markers-and-anti-candida-cytokines-expression-in-mice-in-response-to-vaginal-infection-of-candida-albicans
#2
Ankit Shroff, Roicy Sequeira, Vainav Patel, K V R Reddy
The data presented here are related to the research article entitled "Knockout of autophagy gene, ATG5 in mice vaginal cells abrogates cytokine response and pathogen clearance during vaginal infection of Candida albicans " (Shroff et al., 2018) [1]. The cited research article describes the role of autophagy in host immune response against C. albicans infection of mice vagina. In this data report wild-type C57BL/6 mice were infected intravaginally with C. albicans . Vaginal cells were analyzed for the expression of autophagy marker genes LC3 & ATG5 and lysosome marker LAMP1 at the transcript and protein level...
June 2018: Data in Brief
https://www.readbyqxmd.com/read/29893049/autophagy-inducers-restore-impaired-autophagy-reduce-apoptosis-and-attenuate-blunted-alveolarization-in-hyperoxia-exposed-newborn-rats
#3
Dan Zhang, Linlin Wu, Yanna Du, Yuting Zhu, Bingting Pan, Xindong Xue, Jianhua Fu
AIM: Autophagy is a common process during development. Abnormal autophagy can impact cell apoptosis. Previous studies have shown that apoptosis is present during bronchopulmonary dysplasia (BPD). However, there is no consensus on the level of coexisting autophagy. This study was designed to investigate the role of autophagy and the effects of autophagy inducers in a BPD model. METHOD: A total of 100 newborn Sprague-Dawley rats were randomly assigned to model and control groups...
June 12, 2018: Pediatric Pulmonology
https://www.readbyqxmd.com/read/29884089/a-multiplexed-assay-that-monitors-effects-of-multiple-compound-treatment-times-reveals-candidate-immune-enhancing-compounds
#4
Ziyan Zhao, Liza Henowitz, Adam Zweifach
We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29880899/dapsone-protects-brain-microvascular-integrity-from-high-fat-diet-induced-ldl-oxidation
#5
Rui Zhan, Mingming Zhao, Ting Zhou, Yue Chen, Weiwei Yu, Lei Zhao, Tao Zhang, Hecheng Wang, Huan Yang, Yinglan Jin, Qihua He, Xiaoda Yang, Xiangyang Guo, Belinda Willard, Bing Pan, Yining Huang, Yingyu Chen, Dehua Chui, Lemin Zheng
Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood-brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular. However, whether DDS has a protective role on brain microvessels during lipid oxidation had yet to be elucidated. We investigated brain microvascular integrity in a high-fat diet (HFD) mouse model...
June 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29799519/atg5-overexpression-is-neuroprotective-and-attenuates-cytoskeletal-and-vesicle-trafficking-alterations-in-axotomized-motoneurons
#6
Tatiana Leiva-Rodríguez, David Romeo-Guitart, Sara Marmolejo-Martínez-Artesero, Mireia Herrando-Grabulosa, Assumpció Bosch, Joaquim Forés, Caty Casas
Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve...
May 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29792268/toward-individual-glomerular-phenotyping-advent-of-precision-medicine-in-kidney-biopsies
#7
Kumar Sharma, Ljiljana Paša-Tolić
The road to precision medicine for nephrology is approaching quickly. In the present volume, the glomerular proteome has now been characterized at a single glomerulus level in mouse and human kidneys. Using the Single-Pot Solid-Phase-enhanced Sample Preparation (SP3) approach the authors demonstrated that LAMP1 is a key lysosomal protein that is increased in glomerular diseases and may play a pathogenic role.
June 2018: Kidney International
https://www.readbyqxmd.com/read/29760085/mda-9-syntenin-regulates-protective-autophagy-in-anoikis-resistant-glioma-stem-cells
#8
Sarmistha Talukdar, Anjan K Pradhan, Praveen Bhoopathi, Xue-Ning Shen, Laura A August, Jolene J Windle, Devanand Sarkar, Frank B Furnari, Webster K Cavenee, Swadesh K Das, Luni Emdad, Paul B Fisher
Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29749495/lin28a-inhibits-lysosome%C3%A2-associated-membrane-glycoprotein-1-protein-expression-in-embryonic-stem-and-bladder-cancer-cells
#9
Peng Pan, Ting Chen, Yanmin Zhang, Zhengyu Qi, Jie Qin, Guanghui Cui, Xin Guo
Tumor cells and embryonic stem cells (ESCs) have similar transcription mechanisms. LIN28A is an important factor in tumor cells and ESCs, it is an inhibitor of intracellular endoplasmic reticulum (ER)‑related protein translation in ESCs. The present study aimed to examine the effects of LIN28A on an ER‑related protein, lysosome‑associated membrane glycoprotein 1 (LAMP1), in human bladder cancer cells and mouse (m)ESCs, using reverse transcription‑quantitative polymerase chain reaction and western blotting to detect the expression of LAMP1 mRNA and protein, respectively, following LIN28A knockdown...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29729668/urmc-099-facilitates-amyloid-%C3%AE-clearance-in-a-murine-model-of-alzheimer-s-disease
#10
Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Gang Zhang, R Lee Mosley, Harris A Gelbard, Howard E Gendelman
BACKGROUND: The mixed lineage kinase type 3 inhibitor URMC-099 facilitates amyloid-beta (Aβ) clearance and degradation in cultured murine microglia. One putative mechanism is an effect of URMC-099 on Aβ uptake and degradation. As URMC-099 promotes endolysosomal protein trafficking and reduces Aβ microglial pro-inflammatory activities, we assessed whether these responses affect Aβ pathobiogenesis. To this end, URMC-099's therapeutic potential, in Aβ precursor protein/presenilin-1 (APP/PS1) double-transgenic mice, was investigated in this model of Alzheimer's disease (AD)...
May 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29725750/characterization-of-the-endolysosomal-system-in-human-chordoma-cell-lines-is-there-a-role-of-lysosomes-in-chemoresistance-of-this-rare-bone-tumor
#11
Dagmar Kolb-Lenz, Robert Fuchs, Birgit Lohberger, Ellen Heitzer, Katharina Meditz, Dominique Pernitsch, Elisabeth Pritz, Andrea Groselj-Strele, Andreas Leithner, Bernadette Liegl-Atzwanger, Beate Rinner
Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes...
May 3, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29706874/sensorimotor-and-neurocognitive-dysfunctions-parallel-early-telencephalic-neuropathology-in-fucosidosis-mice
#12
Stijn Stroobants, Heike Wolf, Zsuzsanna Callaerts-Vegh, Thomas Dierks, Torben Lübke, Rudi D'Hooge
Fucosidosis is a lysosomal storage disorder (LSD) caused by lysosomal α-L-fucosidase deficiency. Insufficient α-L-fucosidase activity triggers accumulation of undegraded, fucosylated glycoproteins and glycolipids in various tissues. The human phenotype is heterogeneous, but progressive motor and cognitive impairments represent the most characteristic symptoms. Recently, Fuca1-deficient mice were generated by gene targeting techniques, constituting a novel animal model for human fucosidosis. These mice display widespread LSD pathology, accumulation of secondary storage material and neuroinflammation throughout the brain, as well as progressive loss of Purkinje cells...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29698908/the-expression-of-autophagy-related-proteins-within-the-corpus-luteum-lifespan-in-pigs
#13
M Grzesiak, A Michalik, A Rak, K Knapczyk-Stwora, A Pieczonka
Autophagy is a cellular process that involves the degradation of intracellular components. Recent studies suggested a role for autophagy in corpus luteum (CL) regression; however, a complete understanding of its contribution to CL function remains unclear. The present research using porcine CLs obtained from gilts at the early (CL1, n = 5), middle (CL2, n = 5), and late (CL3, n = 5) luteal phase of the estrous cycle aimed to assess the incidence of autophagy during CL development. The stages of collected CLs were verified through morphological analysis and intraluteal progesterone concentration...
July 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29695488/characterization-of-lamp1-labeled-nondegradative-lysosomal-and-endocytic-compartments-in-neurons
#14
Xiu-Tang Cheng, Yu-Xiang Xie, Bing Zhou, Ning Huang, Tamar Farfel-Becker, Zu-Hang Sheng
Despite widespread distribution of LAMP1 and the heterogeneous nature of LAMP1-labeled compartments, LAMP1 is routinely used as a lysosomal marker, and LAMP1-positive organelles are often referred to as lysosomes. In this study, we use immunoelectron microscopy and confocal imaging to provide quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles do not contain detectable lysosomal hydrolases including cathepsins D and B and glucocerebrosidase...
April 25, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29683502/the-c-terminus-of-the-amelogenin-peptide-influences-the-proliferation-of-human-bone-marrow-mesenchymal-stem-cells
#15
Ryo Kunimatsu, Tetsuya Awada, Yuki Yoshimi, Kazuyo Ando, Naoto Hirose, Yuki Tanne, Keisuke Sumi, Kotaro Tanimoto
BACKGROUND: Amelogenins are a family of enamel matrix proteins that are important for formation of enamel. Amelogenins may induce division of mesenchymal stem cells (MSCs), among others. Recently, the C-terminus of the amelogenin peptide (AMG-CP) has been shown to enhance the proliferation of cementoblast lineage cells. The role of the amelogenin peptide on the proliferation of human MSCs and related alterations in the intracellular signaling pathway were studied. METHODS: MSCs were exposed to AMG-CP in vitro...
April 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29679260/slow-release-of-hiv-1-protein-nef-from-vesicle-like-structures-is-inhibited-by-cytosolic-calcium-elevation-in-single-human-microglia
#16
Matjaž Stenovec, Eva Lasič, Pia Pužar Dominkuš, Saša Trkov Bobnar, Robert Zorec, Metka Lenassi, Marko Kreft
Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tagged with green fluorescent protein (Nef.GFP) to biochemically and microscopically identify Nef.GFP-associated cellular compartments and examine their mobility and Nef release from cultured cells...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29672446/the-effects-of-treadmill-exercise-on-autophagy-in-hippocampus-of-app-ps1-transgenic-mice
#17
Na Zhao, Xianliang Zhang, Chenghui Song, Youcai Yang, Biao He, Bo Xu
The β-amyloid (Aβ) deposition is one of the major pathological hallmark of Alzheimer's disease. Dysfunction in autophagy has been reported to lead to the Aβ deposition. The current study aimed to investigate the effects of treadmill exercise on autophagy activity and the Aβ deposition and to demonstrate whether exercise-induced reduction in the Aβ deposition was associated with changes in autophagy activity. APP/PS1 transgenic mice were divided into transgenic sedentary (TG-SED, n=12) and transgenic exercise (TG-EXE, n=12) groups...
July 4, 2018: Neuroreport
https://www.readbyqxmd.com/read/29668857/de-novo-mutations-of-the-atp6v1a-gene-cause-developmental-encephalopathy-with-epilepsy
#18
Anna Fassio, Alessandro Esposito, Mitsuhiro Kato, Hirotomo Saitsu, Davide Mei, Carla Marini, Valerio Conti, Mitsuko Nakashima, Nobuhiko Okamoto, Akgun Olmez Turker, Burcu Albuz, C Nur Semerci Gündüz, Keiko Yanagihara, Elisa Belmonte, Luca Maragliano, Keri Ramsey, Chris Balak, Ashley Siniard, Vinodh Narayanan, Chihiro Ohba, Masaaki Shiina, Kazuhiro Ogata, Naomichi Matsumoto, Fabio Benfenati, Renzo Guerrini
V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p...
June 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29659804/high-content-screen-for-modifiers-of-niemann-pick-type-c-disease-in-patient-cells
#19
Emily K Pugach, McKenna Feltes, Randal J Kaufman, Daniel S Ory, Anne G Bang
Niemann-Pick type C (NPC) disease is a rare lysosomal storage disease caused primarily by mutations in NPC1. NPC1 encodes the lysosomal cholesterol transport protein NPC1. The most common NPC1 mutation is a missense mutation (NPC1I1061T) that causes misfolding and rapid degradation of mutant protein in the endoplasmic reticulum. Cholesterol accumulates in enlarged lysosomes as a result of decreased levels of lysosomal NPC1I1061T protein in patient cells. There is currently no cure or FDA-approved treatment for patients...
June 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29655686/physakengose-g-induces-apoptosis-via-egfr-mtor-signaling-and-inhibits-autophagic-flux-in-human-osteosarcoma-cells
#20
Hua Lin, Chao Zhang, Hao Zhang, Yuan-Zheng Xia, Chuan-Yang Zhang, Jie Luo, Lei Yang, Ling-Yi Kong
BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. PURPOSE: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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