2012
Activation 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
2009
Genetic and pharmacologic manipulation of vacuolar ATPase: Effects on zymogen activation in pancreatic acini
Kolodecik T, Gorelick F, Thrower E. Genetic and pharmacologic manipulation of vacuolar ATPase: Effects on zymogen activation in pancreatic acini. Open Access Animal Physiology 2009, Volume 1: 1-11. PMID: 21572923, PMCID: PMC3092382, DOI: 10.2147/oaap.s7252.Peer-Reviewed Original ResearchZymogen activationVacuolar ATPaseATP-dependent proton pumpTreatment of cellsGenetic approachesE subunitAcinar cellsProton pumpPancreatic acinar cellsPancreatitis responsesDigestive enzymesAcute pancreatitisPremature activationVATPaseSiRNAATPaseActivationSalicylihalamideCellsRecent studiesOrthologuesBaseline levelsHigh dosesPharmacologic manipulationAmylase secretionThe Acinar Cell and Early Pancreatitis Responses
Gorelick FS, Thrower E. The Acinar Cell and Early Pancreatitis Responses. Clinical Gastroenterology And Hepatology 2009, 7: s10-s14. PMID: 19896090, PMCID: PMC3073378, DOI: 10.1016/j.cgh.2009.07.036.Peer-Reviewed Original ResearchConceptsAcinar cellsAcid loadForms of pancreatitisAcute acid loadSpecific calcium channelsInhibition of secretionPathologic responseAcute pancreatitisPancreatic acinar cellsPathological elevationAbnormal calciumPancreatitis eventsCalcium-dependent phosphataseAlcohol abuseCalcium channelsHarmful stimuliSmall intestineCalcium releasePancreatitisTrypsinogen activationPancreatitis responsesCalcium occursSpecific intracellular signalsActivationIntracellular signalsReducing 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
Protein kinase C in the pancreatic acinar cell
Gorelick F, Pandol S, Thrower E. Protein kinase C in the pancreatic acinar cell. Journal Of Gastroenterology And Hepatology 2008, 23: s37-s41. PMID: 18336661, DOI: 10.1111/j.1440-1746.2007.05282.x.Peer-Reviewed Original ResearchConceptsProtein kinase CKinase CCell-free reconstitution systemPancreatic acinar cellsAcinar cellsPathological responseSpecific PKC isoformsPathogenesis of pancreatitisReconstitution systemCellular eventsPKC isoformsActivation of proteasesApical secretionProtease activationCell eventsInflammatory mediatorsAcute pancreatitisPathological activationSupraphysiological concentrationsPancreatitisPathological effectsPancreatic aciniCholecystokininCellsActivation
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 microscope
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 bafilomycin
2003
Alcohol and Zymogen Activation in the Pancreatic Acinar Cell
Gorelick FS. Alcohol and Zymogen Activation in the Pancreatic Acinar Cell. Pancreas 2003, 27: 305-310. PMID: 14576492, DOI: 10.1097/00006676-200311000-00006.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsSupraphysiologic concentrationsAcute pancreatitisAbility of alcoholMechanism of sensitizationEarly featureIsolated aciniCholecystokininPancreatic aciniInduced activationSensitizationPancreatitisAciniZymogen activationActivationLysosomal markersGranule compartmentCellsActivation of zymogensEffect 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
Alcohols 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
2000
EARLY TRYPSINOGEN ACTIVATION IN ACUTE PANCREATITIS
Lerch M, Gorelick F. EARLY TRYPSINOGEN ACTIVATION IN ACUTE PANCREATITIS. Medical Clinics Of North America 2000, 84: 549-563. PMID: 10872413, DOI: 10.1016/s0025-7125(05)70239-x.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 activationCompartmentsActivationZymogen proteolysis within the pancreatic acinar cell is associated with cellular injury
Grady T, Mah’Moud M, Otani T, Rhee S, Lerch MM, Gorelick FS. Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. American Journal Of Physiology 1998, 275: g1010-g1017. PMID: 9815031, DOI: 10.1152/ajpgi.1998.275.5.g1010.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsCellular injuryForms of pancreatitisAcinar cell injuryTrypsinogen activation peptideSecretagogue treatmentPathological activationCell injuryInjuryIsolated aciniHyperstimulationBombesin treatmentPancreatic aciniTrypsinogen processingImmunofluorescence studiesBombesin stimulationAciniCA1TreatmentDigestive zymogensActivationCellsZymogen activationZymogen processing
1993
Characterization of cAMP‐dependent protein kinase activation by CCK in rat pancreas
Marino C, Leach S, Schaefer J, Miller L, Gorelick F. Characterization of cAMP‐dependent protein kinase activation by CCK in rat pancreas. FEBS Letters 1993, 316: 48-52. PMID: 7678554, PMCID: PMC2830555, DOI: 10.1016/0014-5793(93)81734-h.Peer-Reviewed Original ResearchConceptsCAMP-dependent protein kinase activityProtein kinase activityKinase activityCAMP second messenger cascadeCAMP-dependent protein kinase activationProtein kinase activationSecond messenger cascadesCellular cAMP levelsKinase activationCAMP cascadeTreatment of aciniMessenger cascadesCellular cAMPCAMP levelsEnzyme secretionCascadeNew sensitive assayRat pancreatic aciniSensitive assayPancreatic aciniActivityHigh concentrationsAciniCellsActivation
1991
Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor
Klueppelberg UG, Gates LK, Gorelick FS, Miller LJ. Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor. Journal Of Biological Chemistry 1991, 266: 2403-2408. PMID: 1989991, DOI: 10.1016/s0021-9258(18)52258-4.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCarbacholCell FractionationChromatography, AffinityChromatography, High Pressure LiquidElectrophoresis, Polyacrylamide GelEnzyme ActivationKineticsMalePancreasPhosphorylationProtein Kinase CRatsRats, Inbred StrainsReceptors, CholecystokininSincalideSolubilityTetradecanoylphorbol AcetateConceptsC activationSodium dodecyl sulfate-polyacrylamide gelsDodecyl sulfate-polyacrylamide gelsProtein kinase C activationPlasma membrane glycoproteinsPhosphorylated MrKinase C activationSulfate-polyacrylamide gelsSerine residuesRegulated mannerAffinity-labeled proteinsMembrane glycoproteinsPhosphorylationReceptor proteinProteinNative formATP poolAffinity resinLectin affinity chromatographyConcentration-dependent mannerDirect activationPancreatic cholecystokinin receptorSubsequent solubilizationReceptorsActivationIntracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin.
Leach SD, Modlin IM, Scheele GA, Gorelick FS. Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin. Journal Of Clinical Investigation 1991, 87: 362-366. PMID: 1985109, PMCID: PMC295064, DOI: 10.1172/jci114995.Peer-Reviewed Original ResearchConceptsPancreatic aciniIntracellular activationCysteine protease inhibitor E64Digestive zymogensDose of cholecystokininRat pancreatic aciniProtease inhibitor E64Acute pancreatitisCholecystokininHigh dosesSerine protease activityAcidic subcellular compartmentsWeak base chloroquineImmunologic techniquesInhibitor E64Protonophore monensinPancreatitisIncubation mediumAciniBase chloroquineActivationIntracellular sitesProtease inhibitor benzamidineCell pelletsElectrophoretic mobility