2021
Ovariectomy Affects Acute Pancreatitis in Mice
Wang M, Gorelick F. Ovariectomy Affects Acute Pancreatitis in Mice. Digestive Diseases And Sciences 2021, 67: 2971-2980. PMID: 34169436, PMCID: PMC8702581, DOI: 10.1007/s10620-021-07116-w.Peer-Reviewed Original ResearchConceptsOvariectomized mouse modelEffects of estradiolOvariectomized miceAcute pancreatitisEstradiol levelsPancreatitis severityMouse modelPancreatic studiesSevere acute injurySerum estradiol levelsMild acute pancreatitisAcute pancreatitis severityEstradiol conditionsHospital mortalityHourly injectionsAcute injuryOvariectomized modelFemale hormonesEstradiol injectionPancreatitisEstradiol depletionCausative roleDisease severityConclusionsThese findingsMice
2019
Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice
Malla SR, Krueger B, Wartmann T, Sendler M, Mahajan UM, Weiss FU, Thiel FG, De Boni C, Gorelick FS, Halangk W, Aghdassi AA, Reinheckel T, Gukovskaya AS, Lerch MM, Mayerle J. Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice. Cellular And Molecular Life Sciences 2019, 77: 1811-1825. PMID: 31363815, PMCID: PMC8221268, DOI: 10.1007/s00018-019-03254-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesAutophagyCeruletideEndosomesMaleMiceMice, Inbred C57BLPancreatitisSecretory VesiclesTrypsinTrypsinogen
2017
Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models
Biczo G, Vegh ET, Shalbueva N, Mareninova OA, Elperin J, Lotshaw E, Gretler S, Lugea A, Malla SR, Dawson D, Ruchala P, Whitelegge J, French SW, Wen L, Husain SZ, Gorelick FS, Hegyi P, Rakonczay Z, Gukovsky I, Gukovskaya AS. Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology 2017, 154: 689-703. PMID: 29074451, PMCID: PMC6369139, DOI: 10.1053/j.gastro.2017.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsArginineAutophagyBile Acids and SaltsCalcium SignalingCeruletideCholine DeficiencyCyclophilin DCyclophilinsDisease Models, AnimalEndoplasmic Reticulum StressEthionineGenetic Predisposition to DiseaseHumansLipid MetabolismMembrane Potential, MitochondrialMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Proton-Translocating ATPasesPancreasPancreatitisPhenotypeRatsTime FactorsTrehaloseConceptsDevelopment of APAcute pancreatitisEndoplasmic reticulum stressLipid metabolismImpaired autophagyMitochondrial dysfunctionAnimal modelsL-arginine-induced pancreatitisTreatment of APCyclophilin D knockout micePathogenesis of APAdministration of trehalosePancreatic ER stressParameters of pancreatitisReticulum stressSevere acute pancreatitisPancreas of miceDifferent animal modelsER stressPrincipal downstream effectorPancreatic injuryPathologic responsePancreatitis tissuesCyclophilin DNormal pancreasBidirectional regulation of Aβ levels by Presenilin 1
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P. Bidirectional regulation of Aβ levels by Presenilin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7142-7147. PMID: 28533411, PMCID: PMC5502639, DOI: 10.1073/pnas.1705235114.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAβ levelsΓ-secretase complexAlzheimer's diseasePresenilin 1Pathogenesis of ADAβ peptidesEndogenous kinaseΒ-amyloid peptidePS1 functionIntramembranous proteinsCatalytic subunitΓ-secretase activityPlaque loadC-terminal fragmentAutophagic degradationPotential therapySer367Selective phosphorylationSequential proteolysisTransgenic micePhosphorylationCultured cellsΒ-secretaseDiseasePhosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion
Bustos V, Pulina MV, Bispo A, Lam A, Flajolet M, Gorelick FS, Greengard P. Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7148-7153. PMID: 28533369, PMCID: PMC5502640, DOI: 10.1073/pnas.1705240114.Peer-Reviewed Original Research
2016
Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
Srinivasan P, Thrower EC, Gorelick FS, Said HM. Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AJP Gastrointestinal And Liver Physiology 2016, 310: g874-g883. PMID: 26999808, PMCID: PMC4888549, DOI: 10.1152/ajpgi.00461.2015.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnion Transport ProteinsBiological TransportCarcinogensCell LineHistonesMiceMice, Inbred C57BLMitochondrial Membrane Transport ProteinsMitochondrial ProteinsNitrosaminesPancreasPromoter Regions, GeneticProtein Processing, Post-TranslationalRNA, MessengerThiamine PyrophosphateTobacco Smoke PollutionConceptsPancreatic acinar cellsThiamin pyrophosphateEffect of NNKSpecific plasma membrane transporterPlasma membrane transportersNormal mitochondrial functionMTPPT proteinHistone modificationsH3K4 trimethylationNuclear RNAH3K9 acetylationHeterogenous nuclear RNAMethylation profilesPromoter activityMitochondrial functionChronic exposureReduced expressionNormal metabolismTranscriptionΑ7 nicotinic acetylcholine receptorAcetylcholine receptorsCigarette smoke toxinsTransportersAcinar cellsUptake process
2014
Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasome
2011
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Mehal W. TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis. Gastroenterology 2011, 141: 358-369. PMID: 21439959, PMCID: PMC3129497, DOI: 10.1053/j.gastro.2011.03.041.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-Inflammatory AgentsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CeruletideCytoskeletal ProteinsDisease Models, AnimalDNAInflammasomesInterleukin-1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNecrosisNeutrophil InfiltrationNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisPneumoniaProtein PrecursorsPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7RNA, MessengerSeverity of Illness IndexSignal TransductionTaurolithocholic AcidToll-Like Receptor 9ConceptsToll-like receptor 9Acute pancreatitisWild-type miceAcinar cell deathPancreatic edemaTaurolithocholic acidDamage-associated molecular pattern receptorsResident immune cellsCell deathImmune cell populationsDevelopment of inflammationInitiation of inflammationCell populationsNew therapeutic strategiesMolecular pattern receptorsDAMP receptorsLung inflammationInflammatory infiltrateTLR9 expressionImmune cellsPancreatic necrosisReceptor 9TLR9 antagonistInflammasome activationPurinergic receptors
2009
Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini
Thrower EC, Wang J, Cheriyan S, Lugea A, Kolodecik TR, Yuan J, Reeve JR, Gorelick FS, Pandol SJ. Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini. Pancreas 2009, 38: 930-935. PMID: 19752773, PMCID: PMC2767410, DOI: 10.1097/mpa.0b013e3181b8476a.Peer-Reviewed Original ResearchMeSH KeywordsAcetophenonesAmylasesAnimalsBenzopyransCalcium-Calmodulin-Dependent Protein KinasesCells, CulturedCholecystokininDose-Response Relationship, DrugEnzyme InhibitorsImmunoblottingIndolesMaleMaleimidesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPancreasPeptide FragmentsProtein Kinase C-deltaRatsRats, Sprague-DawleyTrypsinogen
2007
Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII
Li Y, Wang P, Xu J, Gorelick F, Yamazaki H, Andrews N, Desir GV. Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII. Biochemical And Biophysical Research Communications 2007, 362: 658-664. PMID: 17720139, PMCID: PMC2194288, DOI: 10.1016/j.bbrc.2007.08.023.Peer-Reviewed Original ResearchConceptsGLUT4 trafficSyt VIIPlasma membraneGLUT4 translocationConstitutive expressionSecretory granule exocytosisSkeletal muscle cellsGLUT4 traffickingRegulated exocytosisVoltage-gated potassium channel Kv1.3Vesicular trafficSynaptotagmin VIIGLUT4 presentPotassium channel Kv1.3Calcium sensorIntracellular compartmentsDeletion resultsGlucose-stimulated insulin secretionChannel Kv1.3Granule exocytosisPancreatic beta cellsChannel activityInsulin secretionPancreatic islet cellsMuscle cells