Search results for " light chain 3"

showing 5 items of 5 documents

Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…

2019

Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…

0301 basic medicineClinical BiochemistryLFQ Label-free quantificationLETM Leucine zipper and EF-hand containing transmembrane proteinmedicine.disease_causeBiochemistryCHX Cycloheximide0302 clinical medicineBNIP3 Bcl-2 interacting protein 3RAPA RapamycinPIK3C3 Class III PI3‐kinasePhosphorylationlcsh:QH301-705.5Neuronslcsh:R5-920PolyUB PolyubiquitinChemistryBAG3OPA1 Optic atrophy 1TOR Serine-Threonine KinasesWIPI1 WD repeat domain phosphoinositide-interacting protein 1ATG Autophagy relatedTFEB Transcription factor EBCell biologyMitochondriasiRNA Small interfering RNADLP1 Dynamin-like protein 1LAMP1 Lysosomal‐associated membrane protein 1PURO Puromycinlcsh:Medicine (General)Protein homeostasisResearch PaperBafA1 Bafilomycin A1LAMP2 Lysosomal‐associated membrane protein 2Proteasome Endopeptidase ComplexRAB18 Member RAS oncogeneTUB TubulinLC3 Light chain 3 proteinOxidative phosphorylationBAG3CTSD Cathepsin DModels BiologicalCell Line03 medical and health sciencesDownregulation and upregulationMacroautophagymedicineAutophagyHumansAdaptationBAG1 Bcl-2-associated athanogene 1BECN1 Beclin1PI3K/AKT/mTOR pathwayAdaptor Proteins Signal TransducingTEM Transmission electron microscopyHsp70 Heat shock protein 70Organic ChemistryAutophagyAutophagosomesmTOR Mammalian target of rapamycinHsp70Oxidative Stress030104 developmental biologyProteostasislcsh:Biology (General)CV CanavanineBAG3 Bcl-2-associated athanogene 3MTT (3-(45-Dimethylthiazol-2-yl)-25-Diphenyltetrazolium Bromide)Apoptosis Regulatory ProteinsLysosomes030217 neurology & neurosurgeryOxidative stressRedox Biology
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RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy

2014

Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, and its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive and depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) are important factors for the coordination of cellular vesicle transport systems, and several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs are associated with autophagy. Employing C. elegans and human primary fibroblasts, we show that RAB3GAP1 and RAB3GAP2, which are components of the TBC domain-free RAB3GAP complex, influence protein aggregation and affect autophagy at basal an…

GTPase-activating proteinlipid dropletsrab3 GTP-Binding ProteinsATG16L1DMSO dimethyl sulfoxideFEZ20302 clinical medicineATG autophagy-relatedPhagosomesDAPI 4’ 6-diamidino-2-phenylindoleSQSTM1 sequestosome 1ATG16L1MAP1LC3 microtubule-associated protein 1 light chain 3GFP green fluorescent protein0303 health sciencesGABARAP GABA(A) receptor-associated proteinGTPase-Activating ProteinsCell biologyRAB3GAP1RAB3GAP2RABGAP RAB GTPase activating proteinATG3autophagyCALCOCO2 calcium binding and coiled-coil domain 2Basic Research PaperseV empty vectorATG8ATG5PBS phosphate-buffered salineBiologyPE phosphatidylethanolamineTBC domain TRE2-BUB2-CDC16 domainBAG3GEF guanine nucleotide exchange factor03 medical and health sciencesC. elegans Caenorhabditis elegansAnimalsHumansCaenorhabditis elegansMolecular Biology030304 developmental biologySirolimusDPH 1 6-diphenyl-1 3 5-hexatrieneproteostasisAutophagyBiological TransportCell BiologyFEZ1Bafi bafilomycin A1FEZ fasciculation and elongation protein zetaNBR1 neighbor of BRCA1 gene 1ProteostasissiRNA small interfering RNABSA bovine serum albuminRabLysosomes030217 neurology & neurosurgeryAutophagy
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MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

PBD Polo box domainMTD maximal tolerance doseCDC25 cell division cycle 25HIF-1α hypoxia-inducible factor 1 αMST microscale thermophoresisIC50 50% inhibition concentrationMFP M phase promoting factorPARP-1 poly(ADP-ribose) polymerase-10302 clinical medicineFOXO forkhead box ONec-1 necrostatin 1CDC2 cell division cycle protein 2 homologGeneral Pharmacology Toxicology and PharmaceuticsMitotic catastropheCDK cyclin-dependent kinase0303 health sciencesChemistryPolo-like kinaseMono-targeted therapyCell cycleBUBR1 budding uninhibited by benzimidazole-related 1Polo box domain030220 oncology & carcinogenesisPLK1 Polo-like kinaseNecroptosisSpindle damagePLK1IHC immunohistochemistryOriginal articleNecroptosisCell cyclePLK1APC/C anaphase-promoting complex/cyclosomePLK3ABC avidin-biotin complexPI propidium iodide03 medical and health sciencesFBS fetal bovine serumPDB Protein Data BankKd the dissociation constantKinase activity030304 developmental biologyAkt/PKB signaling pathwayCell growthlcsh:RM1-950LC3 light chain 3lcsh:Therapeutics. PharmacologyCancer researchDAPKs death-associated protein kinase3-MA 3-methyladenineDAPI 4′6-diamidino-2-phenylindoleSAC spindle assembly checkpointActa Pharmaceutica Sinica B
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Anti-inflammatory Function of High-Density Lipoproteins via Autophagy of IκB Kinase

2015

Background & Aims: Plasma levels of high-density lipoprotein (HDL) cholesterol are frequently found decreased in patients with inflammatory bowel disease (IBD). Therefore, and because HDL exerts anti-inflammatory activities, we investigated whether HDL and its major protein component apolipoprotein A-I (apoA-I) modulate mucosal inflammatory responses in vitro and in vivo. Methods: The human intestinal epithelial cell line T84 was used as the in vitro model for measuring the effects of HDL on the expression and secretion of tumor necrosis factor (TNF), interleukin-8 (IL-8), and intracellular adhesion molecule (ICAM). Nuclear factor-κB (NF-κB)-responsive promoter activity was studied by …

WT wild typeApolipoprotein BEMSA electrophoretic mobility shift assayMPO myeloperoxidaseIκB kinaseDSS dextran sodium sulphatemTOR the mammalian target of rapamycinRT-PCR real-time polymerase chain reactionNF-κBchemistry.chemical_compound540 ChemistryApoA-I apolipoprotein A-I10038 Institute of Clinical ChemistryOriginal ResearchTNF tumor necrosis factorbiologyIBD inflammatory bowel diseaseChemistryGastroenterologyMyeloperoxidase10076 Center for Integrative Human PhysiologyMEICS murine endoscopic index of colitis severityTumor necrosis factor alphalipids (amino acids peptides and proteins)3-MA 3-methyl adenineNF-κB nuclear factor κBHDL high-density lipoproteinLC3II light chain 3 IIPBS phosphate-buffered salinep-IKK phosphorylated IκB kinase610 Medicine & healthICAM intracellular adhesion molecule246-Trinitrobenzenesulfonic acidTg transgenicmedicineAutophagyCD Crohn’s disease2715 GastroenterologyColitislcsh:RC799-869KO knockoutHepatologyApolipoprotein A-IAutophagyInflammatory Bowel DiseaseTNBS 246-trinitrobenzenesulfonic acidmedicine.diseaseMolecular biologyIL interleukinsiRNA small interfering RNAPI-3 phosphatidylinositol-3Immunologybiology.protein2721 Hepatologylcsh:Diseases of the digestive system. GastroenterologyPFA paraformaldehydeLipoproteinDAPI 4′6-diamidino-2-phenylindoleCMGH Cellular and Molecular Gastroenterology and Hepatology
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Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

2015

Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed--in contrast to viable parasites--that apoptotic-like parasites enter an LC3(+), autophagy-like compartment. The compartm…

log.ph logarithmic phaseT-LymphocytesApoptosisMACS magnetic-associated cell sortingMacrophageMFI mean fluorescence intensityLeishmaniasisMOI multiplicity of infectionanti-inflammatoryLeishmaniaeducation.field_of_studyPhagocytesCFSE carboxyfluorescein succinimidyl esterTGFB transforming growth factorAcquired immune systemapoptotic-like LeishmaniaPS phosphatidylserinehuman primary macrophagesCell biologyβ; TT tetanus toxoidCorrigendumProgrammed cell deathautophagyPopulationAntigen presentationANXA5 annexin VBasic Science Research PapersBiologyPhagocytosisCM complete mediumMAP1LC3/LC3 microtubule-associated protein 1 light chain 3AnimalsHumansMHC major histocompatibility complexIF immunofluorescenceeducationMolecular Biologyimmune evasionPBMCs peripheral blood mononuclear cellsT-cell proliferationIntracellular parasiteMacrophagesstat.ph stationary phaseAutophagyLm LeishmaniaCell BiologyLeishmaniabiology.organism_classificationIL interleukinLAP LC3-associated phagocytosisLAPhMDM human monocyte derived macrophageAutophagy
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