2020
TRPV4 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
2019
Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.
Gukovskaya AS, Gorelick FS, Groblewski GE, Mareninova OA, Lugea A, Antonucci L, Waldron RT, Habtezion A, Karin M, Pandol SJ, Gukovsky I. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas 2019, 48: 459-470. PMID: 30973461, PMCID: PMC6461375, DOI: 10.1097/mpa.0000000000001298.Peer-Reviewed Original ResearchConceptsOrganelle dysfunctionCell death responseSecretion of proteinsAcinar cell homeostasisOrganelle disordersNascent proteinsDysfunctional organellesDeath responseAccessory proteinsVesicular compartmentsEndosomal pathwayCell homeostasisAcute pancreatitisEndoplasmic reticulumProtein synthesisCells triggersPancreatic acinar cellsLethal inflammatory diseaseDigestive enzymesCell constituentsRecent insightsDistinct mechanismsProteinOrganellesAcinar cell injury
2018
Chapter 39 Structure-Function Relationships in the Pancreatic Acinar Cell
Gorelick F, Pandol S, Jamieson J. Chapter 39 Structure-Function Relationships in the Pancreatic Acinar Cell. 2018, 869-894. DOI: 10.1016/b978-0-12-809954-4.00039-6.Peer-Reviewed Original ResearchProtein synthesisEnzyme precursorsRodent acinar cellsAcinar cellsZymogen granulesCritical physiologic functionsSecretion of enzymesStructure-function relationshipsMajor cell typesCellular functionsCell biologistsVesicular transportCell signalingGolgi complexHuman acinar cellsPhysiologic functionEndoplasmic reticulumDuct cellsCell organellesPancreatic acinar cellsCell typesEnzyme proteinDigestive enzymesEnzymeMajor physiologic function
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
Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells
Srinivasan P, Thrower EC, Loganathan G, Balamurugan AN, Subramanian VS, Gorelick FS, Said HM. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells. PLOS ONE 2015, 10: e0143575. PMID: 26633299, PMCID: PMC4669105, DOI: 10.1371/journal.pone.0143575.Peer-Reviewed Original ResearchConceptsHuman pancreatic acinar cellsPancreatic acinar cellsNormal cellular functionThiamin uptakeTHTR-1Chronic exposureMurine pancreatic acinar cellsThiamin uptake processCellular functionsAcinar cellsThiamin pyrophosphokinaseMolecular biologyThiamin transporter-1Mouse pancreatic acinar cellsSpecific carrier-mediated processMitochondrial dysfunctionTHTR-2Chronic nicotine exposureTransporter 1Oxidative stressProteinExpressionNicotine impairsUptake processNicotine exposureEarly to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells
Messenger SW, Thomas D, Cooley MM, Jones EK, Falkowski MA, August BK, Fernandez LA, Gorelick FS, Groblewski GE. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells. Cellular And Molecular Gastroenterology And Hepatology 2015, 1: 695-709. PMID: 26618189, PMCID: PMC4657148, DOI: 10.1016/j.jcmgh.2015.08.002.Peer-Reviewed Original ResearchEarly endosomesRecycling endosomesEndosomal traffickingLate endosomesDominant-negative Rab11a mutantCellular damage responseAssociated membrane proteinLysosome-Associated Membrane ProteinsPIKfyve inhibitionApical traffickingPIKfyve activityEndosomal systemCCK-8Damage responseMembrane proteinsPlasma membraneAcinar cellsPIKfyvePharmacological inhibitorsPancreatic acinar cellsTraffickingEndosomesZymogen activationAdenoviral overexpressionCellular death
2014
Low pH enhances connexin32 degradation in the pancreatic acinar cell
Reed AM, Kolodecik T, Husain SZ, Gorelick FS. Low pH enhances connexin32 degradation in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2014, 307: g24-g32. PMID: 24812055, PMCID: PMC4080162, DOI: 10.1152/ajpgi.00010.2014.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsGap junctionsGap junctional intercellular communicationIntercellular communicationRat pancreatic acinar cellsPredominant gap junction proteinExtracellular pHAcute pancreatitisJunctional intercellular communicationClinical conditionsGap junction proteinJunction proteinsGap junctional intracellular communicationAutophagic pathwayFirst evidenceCellsIntracellular communicationConnexin32Pancreatitis
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
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 hyperstimulationChapter 49 Structure–function Relationships in the Pancreatic Acinar Cell
Gorelick F, Jamieson J. Chapter 49 Structure–function Relationships in the Pancreatic Acinar Cell. 2012, 1341-1360. DOI: 10.1016/b978-0-12-382026-6.00049-x.Peer-Reviewed Original ResearchProtein synthesisZymogen granulesAcinar cellsSecretion of enzymesStructure-function relationshipsNascent proteinsVesicular transportCell signalingEnzyme precursorsGolgi complexEndoplasmic reticulumPancreatic acinar cellsDigestive enzymesEnzymeModel systemExport protein synthesisVectorial mannerApical regionProteinCellsHormonal routesGranulesDigestionDietary proteinExocytosis
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
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
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 activationProtein 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
‘You're Heading in the Right Direction’ An Interview with Dr. Fred Gorelick
Gorelick F. ‘You're Heading in the Right Direction’ An Interview with Dr. Fred Gorelick. Pancreatology 2007, 7: 93-95. PMID: 17541303, DOI: 10.1159/000103357.Peer-Reviewed Original ResearchCaerulein-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