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
2009
The 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 concentrationsNew Insights Into the Mechanisms of Pancreatitis
Gaisano HY, Gorelick FS. New Insights Into the Mechanisms of Pancreatitis. Gastroenterology 2009, 136: 2040-2044. PMID: 19379751, DOI: 10.1053/j.gastro.2009.04.023.Peer-Reviewed Original Research
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 ResearchConceptsAcute 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
Cyclic 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
2006
Vacuolar adenosine triphosphatase and pancreatic acinar cell function
Gorelick FS, Shugrue CA, Kolodecik TR, Thrower EC. Vacuolar adenosine triphosphatase and pancreatic acinar cell function. Journal Of Gastroenterology And Hepatology 2006, 21: s18-s21. PMID: 16958663, DOI: 10.1111/j.1440-1746.2006.04576.x.Peer-Reviewed Original Research
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 ResearchEffects of pancreatic duct ligation on pancreatic response to bombesin
Otani T, Matsukura A, Takamoto T, Seyama Y, Shimizu Y, Shinomiya M, Usui H, Gorelick FS, Makuuchi M. Effects of pancreatic duct ligation on pancreatic response to bombesin. AJP Gastrointestinal And Liver Physiology 2005, 290: g633-g639. PMID: 16293654, DOI: 10.1152/ajpgi.00377.2005.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
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
1999
ETIOPATHOGENESIS OF ACUTE PANCREATITIS
Karne S, Gorelick F. ETIOPATHOGENESIS OF ACUTE PANCREATITIS. Surgical Clinics Of North America 1999, 79: 699-710. PMID: 10470320, DOI: 10.1016/s0039-6109(05)70036-0.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAlcohol DrinkingAnimalsCholelithiasisCytokinesEnzyme PrecursorsHumansPancreatitisConceptsAcute pancreatitisCourse of APPotent proteolytic enzymesCapillary leak syndromeAcinar cellsPreliminary clinical studySpecific clinical settingsSystemic complicationsLeak syndromeCytokine inhibitorsInflammatory moleculesCascade of eventsInflammatory cellsPancreatic edemaVasoactive moleculesClinical studiesParticular neutrophilsPancreatitisFurther secretionClinical settingNitric oxideComplement systemCytokinesPremature activationImmediate releaseMechanisms of intracellular zymogen activation
Gorelick F, Otani T. Mechanisms of intracellular zymogen activation. Best Practice & Research Clinical Gastroenterology 1999, 13: 227-240. PMID: 11030603, DOI: 10.1053/bega.1999.0021.Peer-Reviewed Original ResearchConceptsTrypsinogen activation peptideAcinar cellsZymogen processingDistinct subcellular compartmentsZymogen activationSerine proteasesIntracellular serine proteaseIntracellular zymogen activationCaerulein-induced pancreatitisAcinar cell compartmentPancreatic acinar cellsAcute pancreatitisSubcellular compartmentsHuman pancreatitisPancreatitisExperimental pancreatitisSupramaximal concentrationsHereditary pancreatitisLow-pH compartmentsPancreatic aciniTrypsinogen activationTrypsinogen processingGenetic diseasesCell pathwaysIntracellular activation
1998
Zymogen 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