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 Research
2010
Molecular and cellular mechanisms of pancreatic injury
Thrower EC, Gorelick FS, Husain SZ. Molecular and cellular mechanisms of pancreatic injury. Current Opinion In Gastroenterology 2010, 26: 484-489. PMID: 20651589, PMCID: PMC3023172, DOI: 10.1097/mog.0b013e32833d119e.Peer-Reviewed Original ResearchConceptsPancreatic injuryCellular mechanismsFibroblast growth factor 21Antiapoptotic effectGrowth factor 21Ameliorate injuryEndoplasmic reticulum stressChronic pancreatitisFactor 21Immune cellsExendin-4Endogenous trypsin inhibitorBile acidsDisease severityInjuryPancreatitisCausative factorsSensitizing factorTrypsinogen activationProtein CReticulum stressTrypsinogen mutationsBcl-2Intracellular eventsUpregulation of proteins
2009
Impaired 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 ResearchReducing 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
2005
Zymogen activation in a reconstituted pancreatic acinar cell system
Thrower EC, de Villalvilla A, Kolodecik TR, Gorelick FS. Zymogen activation in a reconstituted pancreatic acinar cell system. AJP Gastrointestinal And Liver Physiology 2005, 290: g894-g902. PMID: 16339296, PMCID: PMC2830560, DOI: 10.1152/ajpgi.00373.2005.Peer-Reviewed Original Research
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
2003
Alcohol and Zymogen Activation in the Pancreatic Acinar Cell
Gorelick FS. Alcohol and Zymogen Activation in the Pancreatic Acinar Cell. Pancreas 2003, 27: 305-310. PMID: 14576492, DOI: 10.1097/00006676-200311000-00006.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsSupraphysiologic concentrationsAcute pancreatitisAbility of alcoholMechanism of sensitizationEarly featureIsolated aciniCholecystokininPancreatic aciniInduced activationSensitizationPancreatitisAciniZymogen activationActivationLysosomal markersGranule compartmentCellsActivation of zymogens
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 speciesMyeloperoxidaseMiceAlcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells
Lu Z, Karne S, Kolodecik T, Gorelick FS. Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2002, 282: g501-g507. PMID: 11842000, PMCID: PMC2830557, DOI: 10.1152/ajpgi.00388.2001.Peer-Reviewed Original Research
1998
Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury
Grady T, Mah’Moud M, Otani T, Rhee S, Lerch MM, Gorelick FS. Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. American Journal Of Physiology 1998, 275: g1010-g1017. PMID: 9815031, DOI: 10.1152/ajpgi.1998.275.5.g1010.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsCellular injuryForms of pancreatitisAcinar cell injuryTrypsinogen activation peptideSecretagogue treatmentPathological activationCell injuryInjuryIsolated aciniHyperstimulationBombesin treatmentPancreatic aciniTrypsinogen processingImmunofluorescence studiesBombesin stimulationAciniCA1TreatmentDigestive zymogensActivationCellsZymogen activationZymogen processing
1993
Influence of Chloroquine on Diet-Induced Pancreatitis
Leach S, Bilchik A, Karapetian O, Gorelick F, Modlin I. Influence of Chloroquine on Diet-Induced Pancreatitis. Pancreas 1993, 8: 64-69. PMID: 7678327, DOI: 10.1097/00006676-199301000-00013.Peer-Reviewed Original ResearchConceptsHigh-dose chloroquineAcidic subcellular compartmentsDiet-induced pancreatitisEthionine-supplemented dietRegular laboratory chowYoung female miceInfluence of chloroquineIntracellular zymogen activationCDE dietAcute pancreatitisContinuous infusionFemale miceLaboratory chowControl animalsPancreatitisExperimental pancreatitisAdditional potential effectsLow-pH compartmentsTrypsinogen contentPancreatic aciniChloroquineAcinar cellsTryptic activityAnimalsDigestive zymogens