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 pancreasHuman 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 ResearchConceptsOrganellar 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
2011
Environmental and Genetic Stressors and the Unfolded Protein Response in Exocrine Pancreatic Function – A Hypothesis
Pandol SJ, Gorelick FS, Lugea A. Environmental and Genetic Stressors and the Unfolded Protein Response in Exocrine Pancreatic Function – A Hypothesis. Frontiers In Physiology 2011, 2: 8. PMID: 21483727, PMCID: PMC3070477, DOI: 10.3389/fphys.2011.00008.Peer-Reviewed Original ResearchProtein responseER stressProtein synthetic machineryUnfolded protein responseDigestive enzymesProtein synthetic capacityRecent findingsAdaptive UPREndoplasmic reticulum stressGenetic stressorsSynthetic machineryMammalian organsEnvironmental stressorsProtein synthesisKey pathwaysUPRReticulum stressExocrine cellsExocrine pancreasSynthetic capacityEnzymePathwayPathologic pathwaysStressorsMachinery
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 proteinsAlcohol Abuse, Endoplasmic Reticulum Stress and Pancreatitis
Pandol SJ, Gorelick FS, Gerloff A, Lugea A. Alcohol Abuse, Endoplasmic Reticulum Stress and Pancreatitis. Digestive Diseases 2010, 28: 776-782. PMID: 21525762, PMCID: PMC3211518, DOI: 10.1159/000327212.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Alcohol abuseChronic pancreatitisEthanol feedingUnfolded protein responseER stressSignificant pathological responseAcinar cellsAfrican American ethnicityEndoplasmic reticulum stressPancreatic manifestationAlcoholic pancreatitisAdaptive unfolded protein responseMinority of individualsChronic inflammationMost individualsPathological responseCommon causePancreatic diseaseApparent diseasePancreatitisBinding protein 1Heavy drinkersExocrine pancreasPancreas
2009
T1834 Role of XBP1 in the Protective Unfolded Protein Response to Limit Chronic Ethanol-Induced Endoplasmic Reticulum Stress and Damage in the Pancreas
Lugea A, Gukovsky I, French S, Gorelick F, Pandol S. T1834 Role of XBP1 in the Protective Unfolded Protein Response to Limit Chronic Ethanol-Induced Endoplasmic Reticulum Stress and Damage in the Pancreas. Gastroenterology 2009, 136: a-589. DOI: 10.1016/s0016-5085(09)62715-3.Peer-Reviewed Original ResearchProtective unfolded protein responseEndoplasmic reticulum stressReticulum stressUnfolded protein responseProtein responsePancreas