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 membraneLAMP1
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 hyperstimulation
2010
Low Extracellular pH Induces Damage in the Pancreatic Acinar Cell by Enhancing Calcium Signaling*
Reed AM, Husain SZ, Thrower E, Alexandre M, Shah A, Gorelick FS, Nathanson MH. Low Extracellular pH Induces Damage in the Pancreatic Acinar Cell by Enhancing Calcium Signaling*. Journal Of Biological Chemistry 2010, 286: 1919-1926. PMID: 21084290, PMCID: PMC3023488, DOI: 10.1074/jbc.m110.158329.Peer-Reviewed Original ResearchConceptsPathogenesis of pancreatitisAcinar cellsRyR inhibitorsLow pHeDevelopment of pancreatitisRyanodine receptor inhibitorPancreatic acinar cellsReceptor inhibitorsClinical conditionsCellular injuryPancreatitisBasolateral regionExocrine pancreasPancreatitis responsesInjurious effectsCalcium signalingPathogenesisInduces damageInhibitorsCellsRyRsInjuryEarly stepsPancreasSensitization
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-DawleyTrypsinogenReducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats
Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS. Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats. Gastroenterology 2009, 137: 1083-1092. PMID: 19454288, PMCID: PMC2736307, DOI: 10.1053/j.gastro.2009.05.041.Peer-Reviewed Original ResearchConceptsAcinar cellsAcute pancreatitisPancreatic acinar cellsSecretagogue-induced pancreatitisAcid loadAcid challengeAcute acid loadKey early eventPancreatic edemaClinical studiesCell injuryPancreatitisAmylase secretionIsolated aciniAbstractTextPhe effectTrypsinogen activationInjuryPancreatitis responsesZymogen activationAIMSEarly eventsRatsActivationRelevant concentrations
2008
The novel protein kinase C isoforms -δ and -ε modulate caerulein-induced zymogen activation in pancreatic acinar cells
Thrower EC, Osgood S, Shugrue CA, Kolodecik TR, Chaudhuri AM, Reeve JR, Pandol SJ, Gorelick FS. The novel protein kinase C isoforms -δ and -ε modulate caerulein-induced zymogen activation in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2008, 294: g1344-g1353. PMID: 18388183, PMCID: PMC2975015, DOI: 10.1152/ajpgi.00020.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCeruletideDose-Response Relationship, DrugEnzyme PrecursorsMalePancreasProtein IsoformsProtein Kinase CRatsRats, Sprague-DawleyConceptsAcute pancreatitisPancreatic acinar cellsAcinar cellsNM caeruleinInitiation of APProtein kinase CCaerulein-induced acute pancreatitisPremature zymogen activationPKC-epsilonSupraphysiological effectsInflammatory mediatorsIsoform-specific PKC inhibitorsPathological secretionPKC-deltaCaerulein administrationPancreatic tissueHormone cholecystokininSupranuclear regionVivo studiesCaerulein stimulationAcinar cell compartmentNovel protein kinase C isoformsActivator of PKCZymogen activation
2007
Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin
Husain SZ, Grant WM, Gorelick FS, Nathanson MH, Shah AU. Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin. AJP Gastrointestinal And Liver Physiology 2007, 292: g1594-g1599. PMID: 17332472, DOI: 10.1152/ajpgi.00500.2006.Peer-Reviewed Original ResearchMeSH KeywordsAmylasesAnimalsCalcineurinCalcineurin InhibitorsCalcium SignalingCells, CulturedCeruletideChelating AgentsChymotrypsinChymotrypsinogenDose-Response Relationship, DrugEgtazic AcidEnzyme ActivationEnzyme InhibitorsMaleOkadaic AcidPancreas, ExocrinePeptidesPhosphoprotein PhosphatasesRatsRats, Sprague-DawleySirolimusTacrolimusTacrolimus Binding ProteinsConceptsZymogen activationPancreatic acinar cellsProtein phosphatase 2BAcinar cellsAmylase secretionCalcineurin inhibitor FK506Calcineurin inhibitory peptidePhosphatase 2BDownstream effectorsChymotrypsin activityInhibitor FK506Isolated pancreatic acinar cellsAcute pancreatitisMicroM FK506Fluo-5FCaerulein stimulationSecretionCalcineurinInhibitory peptidesEnzyme secretionActivationCellsFK506Confocal microscopeScanning confocal microscopeCyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in pancreatic acini
Chaudhuri A, Husain SZ, Kolodecik TR, Grant WM, Gorelick FS. Cyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in pancreatic acini. AJP Gastrointestinal And Liver Physiology 2007, 292: g1403-g1410. PMID: 17234888, PMCID: PMC2975017, DOI: 10.1152/ajpgi.00478.2005.Peer-Reviewed Original ResearchConceptsProtein kinaseZymogen activationCAMP-dependent protein kinaseStimulation of PKACyclic AMP-dependent protein kinasePancreatic acinar cellsAMP-dependent protein kinaseApical actin cytoskeletonCAMP-binding proteinsRole of PKAMuscarinic agonist carbacholIntracellular zymogen activationSupraphysiological concentrationsCAMP-dependent pathwayActin cytoskeletonApical cytoskeletonPhenotypic responsesPKA responseAgonist carbacholCarbachol-induced activationAcinar cellsDecreased secretionEpacCAMP pathwayPancreatic acini
2005
Zymogen activation in a reconstituted pancreatic acinar cell system
Thrower EC, de Villalvilla A, Kolodecik TR, Gorelick FS. Zymogen activation in a reconstituted pancreatic acinar cell system. AJP Gastrointestinal And Liver Physiology 2005, 290: g894-g902. PMID: 16339296, PMCID: PMC2830560, DOI: 10.1152/ajpgi.00373.2005.Peer-Reviewed Original ResearchThe ryanodine receptor mediates early zymogen activation in pancreatitis
Husain SZ, Prasad P, Grant WM, Kolodecik TR, Nathanson MH, Gorelick FS. The ryanodine receptor mediates early zymogen activation in pancreatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 14386-14391. PMID: 16186498, PMCID: PMC1242288, DOI: 10.1073/pnas.0503215102.Peer-Reviewed Original Research
2004
Vacuolar ATPase Regulates Zymogen Activation in Pancreatic Acini*
Waterford SD, Kolodecik TR, Thrower EC, Gorelick FS. Vacuolar ATPase Regulates Zymogen Activation in Pancreatic Acini*. Journal Of Biological Chemistry 2004, 280: 5430-5434. PMID: 15582989, PMCID: PMC2846595, DOI: 10.1074/jbc.m413513200.Peer-Reviewed Original ResearchMeSH KeywordsAmylasesAnimalsCalciumCarbacholCell MembraneCells, CulturedCeruletideChloroquineChymotrypsinEnzyme ActivationEnzyme PrecursorsHydrogen-Ion ConcentrationMacrolidesMaleMonensinPancreasProtein SubunitsProtein TransportRatsRats, Sprague-DawleySolubilityThapsigarginTrypsinVacuolar Proton-Translocating ATPasesConceptsPancreatic acinar cellsSupramaximal concentrationsPancreatic aciniAcinar cellsVacuolar ATPase inhibitor bafilomycinConcentration-dependent mannerAcute pancreatitisEffects of agentsATPase inhibitor bafilomycinConcentration-dependent translocationWeak base chloroquineCaerulein stimulationIntracellular pHConcanamycin AChymotrypsin activationActivationBase chloroquineV-ATPase activationInhibitor bafilomycinEffects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell
Chaudhuri A, Kolodecik TR, Gorelick FS. Effects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2004, 288: g235-g243. PMID: 15458924, PMCID: PMC2975016, DOI: 10.1152/ajpgi.00334.2004.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsSecretion of amylaseAcinar cellsCell injuryIntracellular cAMPForms of pancreatitisParameters of injuryAcinar cell injuryCholinergic agonist carbacholEnzyme secretionRat pancreatic acinar cellsAcute pancreatitisZymogen activationAgonist carbacholSupraphysiological concentrationsCellular injuryCarbacholInjuryPancreatic aciniCAMP productionUnstimulated aciniSecretionCellular cAMPPhysiological concentrationsPancreatitis
2003
Effect of ligands that increase cAMP on caerulein-induced zymogen activation in pancreatic acini
Lu Z, Kolodecik TR, Karne S, Nyce M, Gorelick F. Effect of ligands that increase cAMP on caerulein-induced zymogen activation in pancreatic acini. AJP Gastrointestinal And Liver Physiology 2003, 285: g822-g828. PMID: 12881228, PMCID: PMC2830556, DOI: 10.1152/ajpgi.00213.2003.Peer-Reviewed Original ResearchConceptsCCK analogue caeruleinEffect of CCKAcinar cellsSupraphysiological concentrationsPancreatic aciniCell cAMP levelsRat pancreatic aciniRp-8-BrPancreatic acinar cellsPathological activationCell-permeable cAMP analogCAMP levelsPhysiological concentrationsPancreatitisCell cAMPCCKZymogen activationActivationCAMP analogPhysiological ligandsAciniCells
2002
Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis
Gukovskaya AS, Vaquero E, Zaninovic V, Gorelick FS, Lusis AJ, Brennan M, Holland S, Pandol SJ. Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis. Gastroenterology 2002, 122: 974-984. PMID: 11910350, DOI: 10.1053/gast.2002.32409.Peer-Reviewed Original ResearchConceptsIntrapancreatic trypsin activationAcute pancreatitisNADPH oxidaseTrypsin activationAdenine Dinucleotide Phosphate OxidaseParenchymal cell injuryExperimental acute pancreatitisNADPH oxidase activityPancreatic acinar tissueDigestive enzymesWestern blot analysisAntineutrophil serumPathologic activationCell injuryPancreatitisExperimental pancreatitisHigh dosesMarked attenuationNeutrophilsAbstractTextAcinar tissuePancreatic homogenatesReactive oxygen speciesMyeloperoxidaseMiceAlcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells
Lu Z, Karne S, Kolodecik T, Gorelick FS. Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2002, 282: g501-g507. PMID: 11842000, PMCID: PMC2830557, DOI: 10.1152/ajpgi.00388.2001.Peer-Reviewed Original Research
2001
Synapsin I is expressed in epithelial cells: localization to a unique trans-Golgi compartment.
Bustos R, Kolen E, Braiterman L, Baines A, Gorelick F, Hubbard A. Synapsin I is expressed in epithelial cells: localization to a unique trans-Golgi compartment. Journal Of Cell Science 2001, 114: 3695-704. PMID: 11707521, DOI: 10.1242/jcs.114.20.3695.Peer-Reviewed Original ResearchConceptsSynapsin ITrans-Golgi compartmentSynaptic vesicle exocytosisProtein kinase ANon-neuronal cell linesBrain synapsin IEpithelial cellsNorthern blot analysisTrafficking pathwaysVesicle exocytosisVesicular compartmentsKinase AMyosin IIGolgi complexLimited proteolysisAnti-synapsin antibodiesPre-synaptic terminalsPeptide mapsBlot analysisCell linesCompartmentsCellsNeural tissueLiver cellsCytoskeleton
2000
Cytoplasmic Vacuole Generation in Rat Isolated Pancreatic Acini Under Secretagogue Hyperstimulation Is Associated with Intracellular Acidification
Otani T, Gorelick F. Cytoplasmic Vacuole Generation in Rat Isolated Pancreatic Acini Under Secretagogue Hyperstimulation Is Associated with Intracellular Acidification. Pancreas 2000, 21: 105-107. PMID: 10881943, DOI: 10.1097/00006676-200007000-00062.Peer-Reviewed Original Research
1998
Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis
Otani T, Chepilko S, Grendell J, Gorelick F. Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. American Journal Of Physiology 1998, 275: g999-g1009. PMID: 9815030, DOI: 10.1152/ajpgi.1998.275.5.g999.Peer-Reviewed Original ResearchConceptsAcinar cell compartmentNumber of vesiclesRecycling endosomesSupranuclear compartmentPancreatic acinar cellsTime-dependent mannerProcessing siteCell compartmentTrypsinogen processingPhysiological levelsZymogen granulesImmunofluorescence studiesCaerulein-induced pancreatitisAcinar cellsActivation peptideTrypsinogen activation peptidePathological activationCompartmentsActivation