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 model
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 mice
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
2006
Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation
Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P. Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 1941-1946. PMID: 16449386, PMCID: PMC1413665, DOI: 10.1073/pnas.0510708103.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCell LineEndopeptidasesGene Expression RegulationHumansMembrane ProteinsMiceMice, KnockoutPhospholipase DPresenilin-1Protein BindingProtein Processing, Post-TranslationalProtein TransportTrans-Golgi NetworkPhospholipase 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
2003
Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
Chakrabarti S, Kobayashi KS, Flavell RA, Marks CB, Miyake K, Liston DR, Fowler KT, Gorelick FS, Andrews NW. Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice. Journal Of Cell Biology 2003, 162: 543-549. PMID: 12925704, PMCID: PMC2173791, DOI: 10.1083/jcb.200305131.Peer-Reviewed Original ResearchConceptsVII-deficient miceAntinuclear antibody responseInflammatory autoimmune diseasePolymyositis/dermatomyositisProgressive muscle weaknessCreatine kinase releaseInflammatory myopathiesAutoimmune myositisMuscle weaknessAutoimmune diseasesAutoimmune disordersExtensive fibrosisAntibody responseCollagen depositionDefective plasma membrane repairMembrane repairTrypanosoma cruzi invasionSkeletal muscleMiceExocytosis of lysosomesCruzi invasionInvasionPlasma membrane repairMouse tissuesLysosomal exocytosis
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 speciesMyeloperoxidaseMice