2017
Human Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis
Lugea A, Waldron RT, Mareninova OA, Shalbueva N, Deng N, Su HY, Thomas DD, Jones EK, Messenger SW, Yang J, Hu C, Gukovsky I, Liu Z, Groblewski GE, Gukovskaya AS, Gorelick FS, Pandol SJ. Human Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis. American Journal Of Pathology 2017, 187: 2726-2743. PMID: 28935577, PMCID: PMC5718097, DOI: 10.1016/j.ajpath.2017.08.017.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsCadaverCell Culture TechniquesCells, CulturedHumansPancreasPancreatitisProteomicsConceptsOrganellar morphologyEndoplasmic reticulum stressProteomic characterizationEndolysosomal functionProteomic analysisMolecular mechanismsMitochondrial depolarizationTaurolithocholic acidPhysiological functionsMuscarinic acetylcholine receptor M3Acute pancreatitis patientsBile acid taurolithocholic acidMacrophage inhibitory factorReticulum stressDigestive enzymesMuscarinic agonist carbacholTumor necrosis factorPhysiological responsesSimilar pathological responsesAcinar preparationsAcinar cell responsesCell viabilityInflammatory mediatorsSimilar mechanismPancreatitis patients
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 aciniPancreatitisCerulein 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-DawleyTrypsinogen
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
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
2006
Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons
Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P. Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 1936-1940. PMID: 16449385, PMCID: PMC1413666, DOI: 10.1073/pnas.0510710103.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkOverexpression of PLD1Mutant neuronsPhospholipase D1Beta-amyloid precursor proteinIntracellular traffickingPS1-deficient cellsPLD enzymatic activityTherapeutic targetNeuronal functionPS1 mutationsOverexpression of WTBetaAPPPrecursor proteinMutant cellsSubcellular localizationNeurite outgrowthPLD1 activitySurface deliveryNeuronsOutgrowth capacityCellsTraffickingEnzymatic activityOverexpression
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
2002
COPII proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre-chylomicron transport vesicle
Siddiqi SA, Gorelick FS, Mahan JT, Mansbach CM. COPII proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre-chylomicron transport vesicle. Journal Of Cell Science 2002, 116: 415-427. PMID: 12482926, DOI: 10.1242/jcs.00215.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesApolipoprotein B-48Apolipoproteins BCells, CulturedChylomicronsCOP-Coated VesiclesEndoplasmic ReticulumEpithelial CellsGolgi ApparatusIntestinal AbsorptionIntestinal MucosaLipid MetabolismMaleMembrane FusionMicroscopy, ElectronMonomeric GTP-Binding ProteinsProtein TransportRatsSaccharomyces cerevisiae ProteinsVesicular Transport ProteinsConceptsPre-chylomicron transport vesicleCOPII proteinsEndoplasmic reticulumTransport vesiclesBudding of vesiclesSucrose density centrifugationNascent proteinsCargo proteinsProtein vesiclesMembrane proteinsGolgi complexProteinase K treatmentProteinSec24VesiclesGolgiSar1Intestinal GolgiDensity centrifugationReticulumK treatmentTriton XSec13/31Rbet1COPII
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
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
Phosphorylation of elongation factor 2 in normal and malignant rat glial cells.
Bagaglio DM, Cheng EH, Gorelick FS, Mitsui K, Nairn AC, Hait WN. Phosphorylation of elongation factor 2 in normal and malignant rat glial cells. Cancer Research 1993, 53: 2260-4. PMID: 8485712.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalcium-Calmodulin-Dependent Protein KinasesCalmodulinCell DivisionCells, CulturedElongation Factor 2 KinaseGliomaMaleNeurogliaPeptide Elongation Factor 2Peptide Elongation FactorsPhosphorylationPrecipitin TestsProtein KinasesRatsRats, Sprague-DawleyTrifluoperazineTumor Cells, CulturedConceptsRat brain white matterNormal glial tissueGlial tissueGlioma cellsC6 cellsC6 rat glioma cellsCaM kinase IIIRat glial cellsFactor 2Rat glioma cellsBrain white matterNormal gliaElongation factor 2Glial cellsRat brainWhite matterTumor tissueBasal levelsIII activityCellular proliferationTissueDependent proteinsCellsEndogenous substratesHomogenates