2021
Ketamine and xylazine effects in murine model of acute pancreatitis
Wang M, Gorelick FS. Ketamine and xylazine effects in murine model of acute pancreatitis. AJP Gastrointestinal And Liver Physiology 2021, 320: g1111-g1122. PMID: 33881355, PMCID: PMC8285583, DOI: 10.1152/ajpgi.00023.2021.Peer-Reviewed Original ResearchConceptsKet/XylAcute pancreatitis inductionPancreatitis inductionNeural pathwaysAcute pancreatitisPancreatitis severityAnesthetic agent administrationPancreatitis responsesMild acute pancreatitisExperimental animal modelsAcute pancreatitis severityAcute pancreatitis outcomesMarkers of autophagyXylazine effectsHourly injectionsC57BL/6 miceFuture studiesAnesthetic agentsAnesthetic combinationMurine modelVivo effectsAnesthesia administrationDisease processAnimal modelsAgent administration
2020
Zinc: Roles in pancreatic physiology and disease
Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020, 20: 1413-1420. PMID: 32917512, PMCID: PMC7572834, DOI: 10.1016/j.pan.2020.08.016.Peer-Reviewed Original ResearchConceptsZinc deficiencyReduced zinc levelsPancreatic injuryChronic pancreatitisAcute pancreatitisIL-1βInflammatory cytokinesGastrointestinal diseasesPancreatic diseaseIntestinal absorptionAnimal modelsMacrophage activationCalcium homeostasisNutritional deficienciesBiologic effectsPancreatic physiologyZinc levelsCellular changesDiseasePreliminary dataPancreatitisInflammationEssential trace elementDeficiencyCytokinesTRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Gorelick F, Nathanson MH. TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells. Journal Of Clinical Investigation 2020, 130: 2199-2201. PMID: 32281947, PMCID: PMC7190901, DOI: 10.1172/jci136525.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsCalcium signalingAcinar cellsPlasma membrane calcium channelsGenetic deletion modelsMembrane calcium channelsCytosolic calcium levelsCell culture systemDeletion modelTransient receptor potential vanilloidPathogenesis of pancreatitisSignalingCulture systemCellsPathwayStimulation pathwayCalcium channels
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 pancreasThe serum protein renalase reduces injury in experimental pancreatitis
Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.m117.789776.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersCalcium SignalingCarbacholCell LineCeruletideEnzyme ActivationFluorescent Antibody Technique, IndirectGene Expression Regulation, EnzymologicHumansHypertensionLigandsMembrane Transport ModulatorsMiceMice, KnockoutMonoamine OxidasePancreasPancreatitisPlasma Membrane Calcium-Transporting ATPasesRecombinant Fusion ProteinsTaurolithocholic AcidConceptsRecombinant human renalaseAcute pancreatitisAcute injuryCell injuryAcinar cell injuryHuman acinar cellsCytosolic calcium levelsPlasma membrane calcium ATPasePancreatitis onsetIschemic injuryWT micePathological increaseHistological changesProtective effectSevere diseaseMurine modelMembrane calcium ATPasePancreatitisCalcium levelsExperimental pancreatitisBile acidsTissue damageRenalaseInjuryCerulein modelHuman Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis
Lugea A, Waldron RT, Mareninova OA, Shalbueva N, Deng N, Su HY, Thomas DD, Jones EK, Messenger SW, Yang J, Hu C, Gukovsky I, Liu Z, Groblewski GE, Gukovskaya AS, Gorelick FS, Pandol SJ. Human Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis. American Journal Of Pathology 2017, 187: 2726-2743. PMID: 28935577, PMCID: PMC5718097, DOI: 10.1016/j.ajpath.2017.08.017.Peer-Reviewed Original ResearchConceptsOrganellar morphologyEndoplasmic reticulum stressProteomic characterizationEndolysosomal functionProteomic analysisMolecular mechanismsMitochondrial depolarizationTaurolithocholic acidPhysiological functionsMuscarinic acetylcholine receptor M3Acute pancreatitis patientsBile acid taurolithocholic acidMacrophage inhibitory factorReticulum stressDigestive enzymesMuscarinic agonist carbacholTumor necrosis factorPhysiological responsesSimilar pathological responsesAcinar preparationsAcinar cell responsesCell viabilityInflammatory mediatorsSimilar mechanismPancreatitis patientsAcademic Pancreas Centers of Excellence: Guidance from a multidisciplinary chronic pancreatitis working group at PancreasFest
Sheth SG, Conwell DL, Whitcomb DC, Alsante M, Anderson MA, Barkin J, Brand R, Cote GA, Freedman SD, Gelrud A, Gorelick F, Lee LS, Morgan K, Pandol S, Singh VK, Yadav D, Wilcox CM, Hart PA. Academic Pancreas Centers of Excellence: Guidance from a multidisciplinary chronic pancreatitis working group at PancreasFest. Pancreatology 2017, 17: 419-430. PMID: 28268158, PMCID: PMC5525332, DOI: 10.1016/j.pan.2017.02.015.Peer-Reviewed Original ResearchConceptsChronic pancreatitisPancreas centerManagement of CPDisease-related morbidityProgressive inflammatory diseaseMultidisciplinary managementSurgical treatmentPancreatic functionInflammatory diseasesMedical treatmentGuidance statementsConsensus opinionPancreatitisAcademic physiciansTreatmentWorking GroupLiterature reviewMorbidityGroupEpidemiologyDiseasePhysiciansDiagnosis
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
2015
Acute Pancreatitis—Progress and Challenges
Afghani E, Pandol SJ, Shimosegawa T, Sutton R, Wu BU, Vege SS, Gorelick F, Hirota M, Windsor J, Lo SK, Freeman ML, Lerch MM, Tsuji Y, Melmed GY, Wassef W, Mayerle J. Acute Pancreatitis—Progress and Challenges. Pancreas 2015, 44: 1195-1210. PMID: 26465949, PMCID: PMC4890478, DOI: 10.1097/mpa.0000000000000500.Peer-Reviewed Original Research
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
2013
Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells
Messenger SW, Thomas DD, Falkowski MA, Byrne JA, Gorelick FS, Groblewski GE. Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2013, 305: g439-g452. PMID: 23868405, PMCID: PMC3761242, DOI: 10.1152/ajpgi.00143.2013.Peer-Reviewed Original ResearchConceptsImmature secretory granulesApical exocytosisTumor protein D52Endosomal compartmentsEndolysosomal compartmentsMinor regulated pathwayZymogen granule formationAcinar cellsEndosomal intermediatesISG maturationSerine 136Phosphorylation sitesTrans-GolgiSecretory pathwayAspartate substitutionContent proteinsRegulatory proteinsBrefeldin ASynaptotagmin-1Molecular componentsPancreatic acinar cellsGranule formationExocytosisLysosomal membraneLAMP1Models of Acute and Chronic Pancreatitis
Lerch MM, Gorelick FS. Models of Acute and Chronic Pancreatitis. Gastroenterology 2013, 144: 1180-1193. PMID: 23622127, DOI: 10.1053/j.gastro.2012.12.043.Peer-Reviewed Original ResearchConceptsChronic pancreatitisModels of AcuteInfluence of inflammationAutoimmune chronic pancreatitisChronic ethanol feedingCombination of lipopolysaccharideMechanisms of pathogenesisAcinar cell responsesHuman diseasesPancreatic cancerSevere diseaseRodent modelsEthanol feedingSupraphysiologic concentrationsPancreatitisPancreatitis modelAnimal modelsTherapeutic interventionsCell responsesDiseaseFurther characterizationEarly stagesAcuteInflammationCholecystokinin
2012
Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses
Alexandre M, Uduman AK, Minervini S, Raoof A, Shugrue CA, Akinbiyi EO, Patel V, Shitia M, Kolodecik TR, Patton R, Gorelick FS, Thrower EC. Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses. AJP Gastrointestinal And Liver Physiology 2012, 303: g696-g704. PMID: 22837343, PMCID: PMC3468532, DOI: 10.1152/ajpgi.00138.2012.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAcetylcholine receptorsCigarette smoke toxinsParameters of pancreatitisPancreatitis responsesTobacco carcinogen 4Acinar cell responsesRat pancreatic aciniSmoke toxinsAcute pancreatitisCigarette smokingIntraperitoneal injectionAcinar cell preparationsClinical studiesLong-term effectsCarcinogen 4Pancreatitis modelAdrenergic receptorsReceptor typesCell responsesTobacco toxinsPyknotic nucleiNNKPancreatic aciniPancreatitisActivation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells
Kolodecik TR, Shugrue CA, Thrower EC, Levin LR, Buck J, Gorelick FS. Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells. PLOS ONE 2012, 7: e41320. PMID: 22844459, PMCID: PMC3402497, DOI: 10.1371/journal.pone.0041320.Peer-Reviewed Original ResearchConceptsProtein kinase AActivation of SACZymogen activationPancreatic acinar cellsSpecific subcellular domainsAcinar cellsActivation of zymogensCerulein-treated cellsSubcellular domainsDownstream targetsKinase ASAC activitySAC inhibitorAdenylyl cyclaseDistinct mechanismsAdenylyl cyclase inhibitorElevates levelsApical regionAmylase secretionCellsActivationAcinar cell vacuolizationCAMPCAMP accumulationCell vacuolizationCerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation
Shugrue C, Alexandre M, de Villalvilla A, Kolodecik TR, Young LH, Gorelick FS, Thrower EC. Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation. AJP Gastrointestinal And Liver Physiology 2012, 303: g723-g732. PMID: 22821946, PMCID: PMC3468535, DOI: 10.1152/ajpgi.00082.2012.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsCells, CulturedCeruletideCyclic AMP-Dependent Protein KinasesEnzyme PrecursorsGene Expression RegulationMaleMetforminOctoxynolPancreasPhosphorylationPyrazolesPyrimidinesRatsRats, Sprague-DawleyRibonucleotidesSodium Dodecyl SulfateConceptsAdenosine monophosphate-activated protein kinaseZymogen activationAMPK activityPancreatic acinar cellsMonophosphate-activated protein kinaseVacuolar ATPase activityAMPK levelsDigestive enzyme zymogensAMPK effectsProtein kinaseProtein kinase levelsE subunitAcinar cellsTime-dependent translocationCompound CCellular modelPancreatitis responsesATPase activityDifferential centrifugationPremature activationChymotrypsin activityActivationInitiating eventSoluble fractionCerulein hyperstimulationSterile Inflammatory Response in Acute Pancreatitis
Hoque R, Malik AF, Gorelick F, Mehal WZ. Sterile Inflammatory Response in Acute Pancreatitis. Pancreas 2012, 41: 353-357. PMID: 22415665, PMCID: PMC3306133, DOI: 10.1097/mpa.0b013e3182321500.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsSterile inflammatory responseAcute pancreatitisInterleukin-1βInflammatory responseExperimental pancreatitisNOD-like receptor protein 3High mobility group box protein 1Toll-like receptor 4Remote organ injuryReceptor protein 3Acinar cellsExperimental acute pancreatitisIL-1 receptorNovel therapeutic targetBox protein 1Necrotic acinar cellsDAMP receptorsShock protein 70Disease resolutionPancreatic injuryOrgan injuryInitial injuryIL-18Pharmacologic antagonism
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 receptorsThe Emerging Role of Smoking in the Development of Pancreatitis
Alexandre M, Pandol SJ, Gorelick FS, Thrower EC. The Emerging Role of Smoking in the Development of Pancreatitis. Pancreatology 2011, 11: 469-474. PMID: 21986098, PMCID: PMC3222114, DOI: 10.1159/000332196.Peer-Reviewed Original ResearchConceptsDevelopment of pancreatitisTobacco smokingChronic pancreatitisAcute pancreatitisCigarette smokingPancreatic cancerBACKGROUND/Cigarette smokeElectronic searchSmokingPancreatitisOnly articlesEmerging RolePancreasNicotineOriginal articlesRiskMetabolitesSpecific constituentsPubMedCancerDiseaseDoseProgression
2010
Molecular and cellular mechanisms of pancreatic injury
Thrower EC, Gorelick FS, Husain SZ. Molecular and cellular mechanisms of pancreatic injury. Current Opinion In Gastroenterology 2010, 26: 484-489. PMID: 20651589, PMCID: PMC3023172, DOI: 10.1097/mog.0b013e32833d119e.Peer-Reviewed Original ResearchConceptsPancreatic injuryCellular mechanismsFibroblast growth factor 21Antiapoptotic effectGrowth factor 21Ameliorate injuryEndoplasmic reticulum stressChronic pancreatitisFactor 21Immune cellsExendin-4Endogenous trypsin inhibitorBile acidsDisease severityInjuryPancreatitisCausative factorsSensitizing factorTrypsinogen activationProtein CReticulum stressTrypsinogen mutationsBcl-2Intracellular eventsUpregulation of proteins
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