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
Ovariectomy 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
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
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 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 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 exposure
2014
Lactate 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 inflammasome
2011
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Mehal W. TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis. Gastroenterology 2011, 141: 358-369. PMID: 21439959, PMCID: PMC3129497, DOI: 10.1053/j.gastro.2011.03.041.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-Inflammatory AgentsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CeruletideCytoskeletal ProteinsDisease Models, AnimalDNAInflammasomesInterleukin-1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNecrosisNeutrophil InfiltrationNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisPneumoniaProtein PrecursorsPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7RNA, MessengerSeverity of Illness IndexSignal TransductionTaurolithocholic AcidToll-Like Receptor 9ConceptsToll-like receptor 9Acute pancreatitisWild-type miceAcinar cell deathPancreatic edemaTaurolithocholic acidDamage-associated molecular pattern receptorsResident immune cellsCell deathImmune cell populationsDevelopment of inflammationInitiation of inflammationCell populationsNew therapeutic strategiesMolecular pattern receptorsDAMP receptorsLung inflammationInflammatory infiltrateTLR9 expressionImmune cellsPancreatic necrosisReceptor 9TLR9 antagonistInflammasome activationPurinergic receptors
2010
Adaptive Unfolded Protein Response Attenuates Alcohol-Induced Pancreatic Damage
Lugea A, Tischler D, Nguyen J, Gong J, Gukovsky I, French SW, Gorelick FS, Pandol SJ. Adaptive Unfolded Protein Response Attenuates Alcohol-Induced Pancreatic Damage. Gastroenterology 2010, 140: 987-997.e8. PMID: 21111739, PMCID: PMC3057335, DOI: 10.1053/j.gastro.2010.11.038.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsApoptosisApoptosis Regulatory ProteinsDisease Models, AnimalDNA-Binding ProteinsEndoplasmic ReticulumEthanolMaleMiceMice, Inbred BALB CMice, KnockoutPancreas, ExocrinePancreatitis, AlcoholicProtein Disulfide-IsomerasesRatsRats, WistarRegulatory Factor X Transcription FactorsStress, PhysiologicalTissue Culture TechniquesTranscription FactorsUnfolded Protein ResponseX-Box Binding Protein 1ConceptsProtein disulfide isomeraseX-box binding protein 1ER stressUPR regulatorOxidation of PDIER protein foldingDisulfide bond formationBinding protein 1Reticulum stress responseDisulfide isomeraseProtein foldingER functionProapoptotic signalsStress responseHuman disordersXBP1 deficiencyAcinar cell deathER dysfunctionCell deathXBP1 levelsAlcohol-induced ER stressPDI levelsProtein 1UPRWild-type miceGamma-secretase activating protein is a therapeutic target for Alzheimer’s disease
He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Greengard P. Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease. Nature 2010, 467: 95-98. PMID: 20811458, PMCID: PMC2936959, DOI: 10.1038/nature09325.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseGamma-secretase activating proteinDisease drugsBlood-brain barrierSevere side effectsΓ-secretase activating proteinPossible new targetsAlzheimer's disease drugsNotch cleavageSide effectsTherapeutic targetActivating proteinHomeostatic functionsAnti-Alzheimer drugsDiseaseNew targetsΓ-secretaseAnticancer drug imatinibProcessing of NotchDrugsDrug imatinibImatinibBrain
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-DawleyTrypsinogenImpaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis
Mareninova OA, Hermann K, French SW, O’Konski M, Pandol SJ, Webster P, Erickson AH, Katunuma N, Gorelick FS, Gukovsky I, Gukovskaya AS. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. Journal Of Clinical Investigation 2009, 119: 3340-3355. PMID: 19805911, PMCID: PMC2769194, DOI: 10.1172/jci38674.Peer-Reviewed Original Research
2008
Molecular basis for pancreatitis
Thrower E, Husain S, Gorelick F. Molecular basis for pancreatitis. Current Opinion In Gastroenterology 2008, 24: 580-585. PMID: 19122498, PMCID: PMC3030809, DOI: 10.1097/mog.0b013e32830b10e6.Peer-Reviewed Original ResearchConceptsChronic pancreatitisAcute pancreatitisPain responseAnimal modelsToll-like receptor 4Transient receptor potential vanilloid subtype 1Specific neural receptorsSevere acute pancreatitisBasic science studiesChymotrypsin CShock protein 70Neural receptorsReceptor 4Chronic diseasesPancreatitisAlcohol abuseReceptor 2Subtype 1Potential treatmentPilot studyProtective mechanismAcinar cellsProtein 70Genetic factorsYear findings
2007
Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII
Li Y, Wang P, Xu J, Gorelick F, Yamazaki H, Andrews N, Desir GV. Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII. Biochemical And Biophysical Research Communications 2007, 362: 658-664. PMID: 17720139, PMCID: PMC2194288, DOI: 10.1016/j.bbrc.2007.08.023.Peer-Reviewed Original ResearchConceptsGLUT4 trafficSyt VIIPlasma membraneGLUT4 translocationConstitutive expressionSecretory granule exocytosisSkeletal muscle cellsGLUT4 traffickingRegulated exocytosisVoltage-gated potassium channel Kv1.3Vesicular trafficSynaptotagmin VIIGLUT4 presentPotassium channel Kv1.3Calcium sensorIntracellular compartmentsDeletion resultsGlucose-stimulated insulin secretionChannel Kv1.3Granule exocytosisPancreatic beta cellsChannel activityInsulin secretionPancreatic islet cellsMuscle cellsPancreatic protease-activated receptors: friend and foe
Gorelick F. Pancreatic protease-activated receptors: friend and foe. Gut 2007, 56: 901. PMID: 17566024, PMCID: PMC1994359, DOI: 10.1136/gut.2006.111245.Peer-Reviewed Original Research