2017
The 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 model
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 vacuolization
2011
The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer
Chung C, Mader CC, Schmitz J, Atladottir J, Fitchev P, Cornwell M, Koleske AJ, Crawford SE, Gorelick F. The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer. Laboratory Investigation 2011, 91: 732-743. PMID: 21339745, PMCID: PMC3084324, DOI: 10.1038/labinvest.2011.8.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaMMP-9 activityHuman pancreatic cancerPancreatic cancerPanIN lesionsHigh-grade PanIN lesionsHuman pancreatic ductal adenocarcinomaPancreatic intraepithelial neoplasmsCancer cellsLow-grade PanIN lesionsMatrix metalloproteinase activationMMP-2 activityPancreatic cancer cellsHuman cancer tissuesShort hairpin RNAPancreatic histologyIntraepithelial neoplasmDuctal adenocarcinomaNormal ductsMMP releaseCancer tissuesMMP-2Metalloproteinase activationInvasive propertiesSpecific MMPs
2009
Reducing 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
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
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 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 zymogens
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
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
1999
Mechanisms 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
1995
Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling
Fern RJ, Hahm MS, Lu HK, Liu LP, Gorelick FS, Barrett PQ. Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling. American Journal Of Physiology 1995, 269: f751-f760. PMID: 8594869, DOI: 10.1152/ajprenal.1995.269.6.f751.Peer-Reviewed Original ResearchConceptsCaMKII activityBovine adrenal glomerulosa cellsDepolarization-induced increaseAdrenal glomerulosa cellsDepolarization-induced Ca2Voltage-gated Ca2Independent CaMKII activityElevated extracellular potassiumDependent protein kinase II (CaMKII) activationCaMKII inhibitor peptideAgonist-induced stimulationAldosterone secretagoguesAngiotensin IIGlomerulosa cellsKinase activityExtracellular potassiumImportance of CaMKIIIntracellular Ca2Dependent protein kinase IIProtein kinase IICell treatmentKN-62Calmodulin antagonistsCell-permeable inhibitorChannel activity
1994
Calcium/calmodulin-dependent protein kinase-II activation in rat pituitary cells in the presence of thyrotropin-releasing hormone and dopamine
Cui ZJ, Gorelick FS, Dannies PS. Calcium/calmodulin-dependent protein kinase-II activation in rat pituitary cells in the presence of thyrotropin-releasing hormone and dopamine. Endocrinology 1994, 134: 2245-2250. PMID: 8156928, DOI: 10.1210/endo.134.5.8156928.Peer-Reviewed Original ResearchConceptsPulses of TRHPRL releaseCaM kinase IIPituitary cellsAnterior pituitary cellsCaM kinase II activityThyrotropin-releasing hormoneRat pituitary cellsCalmodulin-dependent protein kinase II activationCalcium/calmodulin-dependent protein kinase II (CaMKII) activationKinase IICalcium/calmodulin-dependent protein kinase IIPretreatment of cellsCalmodulin-dependent protein kinase IIBasal valuesKinase II activityLack of responsivenessKinase activityIntracellular Ca2TRHProtein kinase IIRat lactotrophsDopamineTRH pulsesLactotrophs
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
1992
Intracellular proteolysis of pancreatic zymogens.
Gorelick FS, Modlin IM, Leach SD, Carangelo R, Katz M. Intracellular proteolysis of pancreatic zymogens. The Yale Journal Of Biology And Medicine 1992, 65: 407-20; discussion 437-40. PMID: 1340058, PMCID: PMC2589730.Peer-Reviewed Original ResearchAnimalsBenzamidinesBiological TransportCarbacholCarboxypeptidase BCarboxypeptidasesCarboxypeptidases ACholecystokininChymotrypsinogenCysteine Proteinase InhibitorsEnzyme ActivationEnzyme PrecursorsHydrogen-Ion ConcentrationLeucineModels, BiologicalPancreasPancreatitisProtein Processing, Post-TranslationalTime FactorsTrypsin Inhibitors