2023
Plasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2021
Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease
Pointer TC, Gorelick FS, Desir GV. Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease. Cells 2021, 10: 2006. PMID: 34440775, PMCID: PMC8391834, DOI: 10.3390/cells10082006.Peer-Reviewed Original ResearchConceptsProsurvival effectAcute cerulein pancreatitisRole of renalaseAnti-inflammatory effectsDisease modelsAcute organ injuryRelevant clinical settingsShortens life expectancyPreclinical disease modelsCell survivalHuman cancer tissuesCancer cell survivalOrgan injuryAcute injuryPancreatic cancerIntestinal diseaseGastrointestinal diseasesRodent modelsCerulein pancreatitisSelect cancersCancer tissuesRenalaseClinical settingTherapeutic agentsExport transportersOvariectomy Affects Acute Pancreatitis in Mice
Wang M, Gorelick F. Ovariectomy Affects Acute Pancreatitis in Mice. Digestive Diseases And Sciences 2021, 67: 2971-2980. PMID: 34169436, PMCID: PMC8702581, DOI: 10.1007/s10620-021-07116-w.Peer-Reviewed Original ResearchConceptsOvariectomized mouse modelEffects of estradiolOvariectomized miceAcute pancreatitisEstradiol levelsPancreatitis severityMouse modelPancreatic studiesSevere acute injurySerum estradiol levelsMild acute pancreatitisAcute pancreatitis severityEstradiol conditionsHospital mortalityHourly injectionsAcute injuryOvariectomized modelFemale hormonesEstradiol injectionPancreatitisEstradiol depletionCausative roleDisease severityConclusionsThese findingsMiceKetamine and xylazine effects in murine model of acute pancreatitis
Wang M, Gorelick FS. Ketamine and xylazine effects in murine model of acute pancreatitis. AJP Gastrointestinal And Liver Physiology 2021, 320: g1111-g1122. PMID: 33881355, PMCID: PMC8285583, DOI: 10.1152/ajpgi.00023.2021.Peer-Reviewed Original ResearchConceptsKet/XylAcute pancreatitis inductionPancreatitis inductionNeural pathwaysAcute pancreatitisPancreatitis severityAnesthetic agent administrationPancreatitis responsesMild acute pancreatitisExperimental animal modelsAcute pancreatitis severityAcute pancreatitis outcomesMarkers of autophagyXylazine effectsHourly injectionsC57BL/6 miceFuture studiesAnesthetic agentsAnesthetic combinationMurine modelVivo effectsAnesthesia administrationDisease processAnimal modelsAgent administration
2020
Zinc: Roles in pancreatic physiology and disease
Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020, 20: 1413-1420. PMID: 32917512, PMCID: PMC7572834, DOI: 10.1016/j.pan.2020.08.016.Peer-Reviewed Original ResearchConceptsZinc deficiencyReduced zinc levelsPancreatic injuryChronic pancreatitisAcute pancreatitisIL-1βInflammatory cytokinesGastrointestinal diseasesPancreatic diseaseIntestinal absorptionAnimal modelsMacrophage activationCalcium homeostasisNutritional deficienciesBiologic effectsPancreatic physiologyZinc levelsCellular changesDiseasePreliminary dataPancreatitisInflammationEssential trace elementDeficiencyCytokines
2019
Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice
Malla SR, Krueger B, Wartmann T, Sendler M, Mahajan UM, Weiss FU, Thiel FG, De Boni C, Gorelick FS, Halangk W, Aghdassi AA, Reinheckel T, Gukovskaya AS, Lerch MM, Mayerle J. Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice. Cellular And Molecular Life Sciences 2019, 77: 1811-1825. PMID: 31363815, PMCID: PMC8221268, DOI: 10.1007/s00018-019-03254-7.Peer-Reviewed Original ResearchAnimal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.
Saloman JL, Albers KM, Cruz-Monserrate Z, Davis BM, Edderkaoui M, Eibl G, Epouhe AY, Gedeon JY, Gorelick FS, Grippo PJ, Groblewski GE, Husain SZ, Lai KKY, Pandol SJ, Uc A, Wen L, Whitcomb DC. Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer. Pancreas 2019, 48: 759-779. PMID: 31206467, PMCID: PMC6581211, DOI: 10.1097/mpa.0000000000001335.Peer-Reviewed Original Research
2018
Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice
Alahmari AA, Sreekumar B, Patel V, Ashat M, Alexandre M, Uduman AK, Akinbiyi EO, Ceplenski A, Shugrue CA, Kolodecik TR, Tashkandi N, Messenger SW, Groblewski GE, Gorelick FS, Thrower EC. Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice. PLOS ONE 2018, 13: e0197362. PMID: 29870540, PMCID: PMC5988302, DOI: 10.1371/journal.pone.0197362.Peer-Reviewed Original ResearchConceptsNNK treatmentHuman acinar cellsNicotinic acetylcholine receptorsTrypsinogen activationAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorIndependent risk factorMarkers of inflammationAcinar cellsΑ7nAChR knockout miceΑ7nAChR activationNeutrophil infiltrationWT miceAcute pancreatitisC57BL/6 miceCigarette smokingPancreatic edemaRisk factorsClinical studiesPancreatitisCigarette smokeKnockout miceExperimental pancreatitisΑ7 isoformPyknotic nuclei
2017
Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models
Biczo G, Vegh ET, Shalbueva N, Mareninova OA, Elperin J, Lotshaw E, Gretler S, Lugea A, Malla SR, Dawson D, Ruchala P, Whitelegge J, French SW, Wen L, Husain SZ, Gorelick FS, Hegyi P, Rakonczay Z, Gukovsky I, Gukovskaya AS. Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology 2017, 154: 689-703. PMID: 29074451, PMCID: PMC6369139, DOI: 10.1053/j.gastro.2017.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsArginineAutophagyBile Acids and SaltsCalcium SignalingCeruletideCholine DeficiencyCyclophilin DCyclophilinsDisease Models, AnimalEndoplasmic Reticulum StressEthionineGenetic Predisposition to DiseaseHumansLipid MetabolismMembrane Potential, MitochondrialMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Proton-Translocating ATPasesPancreasPancreatitisPhenotypeRatsTime FactorsTrehaloseConceptsDevelopment of APAcute pancreatitisEndoplasmic reticulum stressLipid metabolismImpaired autophagyMitochondrial dysfunctionAnimal modelsL-arginine-induced pancreatitisTreatment of APCyclophilin D knockout micePathogenesis of APAdministration of trehalosePancreatic ER stressParameters of pancreatitisReticulum stressSevere acute pancreatitisPancreas of miceDifferent animal modelsER stressPrincipal downstream effectorPancreatic injuryPathologic responsePancreatitis tissuesCyclophilin DNormal pancreasThe 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 modelBidirectional regulation of Aβ levels by Presenilin 1
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P. Bidirectional regulation of Aβ levels by Presenilin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7142-7147. PMID: 28533411, PMCID: PMC5502639, DOI: 10.1073/pnas.1705235114.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAβ levelsΓ-secretase complexAlzheimer's diseasePresenilin 1Pathogenesis of ADAβ peptidesEndogenous kinaseΒ-amyloid peptidePS1 functionIntramembranous proteinsCatalytic subunitΓ-secretase activityPlaque loadC-terminal fragmentAutophagic degradationPotential therapySer367Selective phosphorylationSequential proteolysisTransgenic micePhosphorylationCultured cellsΒ-secretaseDiseasePhosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion
Bustos V, Pulina MV, Bispo A, Lam A, Flajolet M, Gorelick FS, Greengard P. Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7148-7153. PMID: 28533369, PMCID: PMC5502640, DOI: 10.1073/pnas.1705240114.Peer-Reviewed Original Research
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 processInhibition of renalase expression and signaling has antitumor activity in pancreatic cancer
Guo X, Hollander L, MacPherson D, Wang L, Velazquez H, Chang J, Safirstein R, Cha C, Gorelick F, Desir GV. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Scientific Reports 2016, 6: 22996. PMID: 26972355, PMCID: PMC4789641, DOI: 10.1038/srep22996.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibodiesApoptosisCarcinoma, Pancreatic DuctalCell Cycle CheckpointsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateMaleMice, NudeMiddle AgedMonoamine OxidasePancreatic NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionXenograft Model Antitumor AssaysConceptsRenalase expressionPancreatic cancerPancreatic ductal adenocarcinoma growthCohort of patientsPancreatic cancer tissuesPancreatic ductal adenocarcinomaPancreatic ductal adenocarcinoma cellsXenograft mouse modelAttractive therapeutic targetDuctal adenocarcinoma cellsTumor cell apoptosisOverall survivalPathogenic roleCell cycle arrestDuctal adenocarcinomaPrognostic makerTumor massMouse modelTherapeutic targetCellular injuryCancer tissuesRenalaseCancerAdenocarcinoma cellsGrowth factor
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 exposure
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 communicationConnexin32PancreatitisLactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasomeAdenylyl cyclases in the digestive system
Sabbatini ME, Gorelick F, Glaser S. Adenylyl cyclases in the digestive system. Cellular Signalling 2014, 26: 1173-1181. PMID: 24521753, PMCID: PMC4441802, DOI: 10.1016/j.cellsig.2014.01.033.Peer-Reviewed Original Research
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 membraneLAMP1Models of Acute and Chronic Pancreatitis
Lerch MM, Gorelick FS. Models of Acute and Chronic Pancreatitis. Gastroenterology 2013, 144: 1180-1193. PMID: 23622127, DOI: 10.1053/j.gastro.2012.12.043.Peer-Reviewed Original ResearchConceptsChronic pancreatitisModels of AcuteInfluence of inflammationAutoimmune chronic pancreatitisChronic ethanol feedingCombination of lipopolysaccharideMechanisms of pathogenesisAcinar cell responsesHuman diseasesPancreatic cancerSevere diseaseRodent modelsEthanol feedingSupraphysiologic concentrationsPancreatitisPancreatitis modelAnimal modelsTherapeutic interventionsCell responsesDiseaseFurther characterizationEarly stagesAcuteInflammationCholecystokinin