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PANCREATITIS-ASSOCIATED PROTEIN-1 SUPPRESSES APOPTOSIS IN CERULEIN-STIMULATED PANCREATIC ACINAR CELLS IN RESPONSE TO NUCLEAR FACTOR-KAPPA B ACTIVATION

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dc.date.accessioned2022-08-19T06:27:03Z-
dc.date.available2022-08-19T06:27:03Z-
dc.date.issued2019-12-
dc.identifier.issn0867-5910-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/189183-
dc.description.abstractPancreatitis is a disease for which there are numerous etiologies but no effective treatments. Although the expression of the pancreatitis-associated protein-1 (PAP-1) serves as a marker for the disease, its biological function is unknown. The present study was carried out to determine if PAP-1 performs a protective role against oxidative stress-induced pancreatic cell death. For this purpose, we used cerulein-stimulated pancreatic acinar AR42J cells as an experimental model of acute pancreatitis. First, we demonstrated that PAP-1 gene expression is increased by cerulein in a dose- and time-dependent manner. In parallel, the level of active nuclear factor kappaB (NF-kappa B) was found to be increased in cells treated with cerulein. To test whether activation of the oxidant-sensitive transcription factor NF-kappa B is mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the primary source of reactive oxygen species, cerulein-stimulated NADPH oxidase activity was suppressed by using the NADPH oxidase inhibitor diphenyleneiodonium and, separately, by anti-sense oligonucleotides directed against NADPH oxidase subunits p22(phox) and p47(phox). We observed that a decrease in NADPH oxidase activity resulted in decreased NF-kappa B activation and decreased PAP-1 gene expression. To determine whether the cerulein-induced NF-kappa B activation involves PAP-1 expression, cells were transfected to overexpress the MAD3 double-point I kappa B alpha mutant. In response, NF-kappa B activation and PAP-1 gene expression were decreased. Lastly, we observed that the cerulein-induced reduction in cell viability and increase in apoptosis are reversed by overexpression of PAP-1 in PAP-1-transfected cells. Taken together, these results support the postulate that PAP-1 inhibits cerulein-induced apoptosis in response to NADPH oxidase-mediated NF-kappa B activation in pancreatic acinar cells.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherPolish Physiological Society-
dc.relation.isPartOfJOURNAL OF PHYSIOLOGY AND PHARMACOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAcinar Cells / drug effects*-
dc.subject.MESHAcinar Cells / pathology-
dc.subject.MESHAcute Disease-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis / physiology-
dc.subject.MESHCell Survival / drug effects-
dc.subject.MESHCells, Cultured-
dc.subject.MESHCeruletide-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHNADPH Oxidases / metabolism-
dc.subject.MESHNF-kappa B / metabolism-
dc.subject.MESHOxidative Stress-
dc.subject.MESHPancreatitis / physiopathology*-
dc.subject.MESHPancreatitis-Associated Proteins / genetics*-
dc.subject.MESHRats-
dc.subject.MESHReactive Oxygen Species / metabolism-
dc.titlePANCREATITIS-ASSOCIATED PROTEIN-1 SUPPRESSES APOPTOSIS IN CERULEIN-STIMULATED PANCREATIC ACINAR CELLS IN RESPONSE TO NUCLEAR FACTOR-KAPPA B ACTIVATION-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorJ H Yu-
dc.contributor.googleauthorJ W Lim-
dc.contributor.googleauthorH Kim-
dc.identifier.doi10.26402/jpp.2019.6.04-
dc.relation.journalcodeJ01711-
dc.identifier.eissn1899-1505-
dc.identifier.pmid32084646-
dc.subject.keywordcerulein-
dc.subject.keywordnicotinamide adenine dinucleotide phosphate oxidase-
dc.subject.keywordnuclear factor-kappa B-
dc.subject.keywordpancreatitis-associated protein-1-
dc.subject.keywordpancreatic acinar cells-
dc.subject.keywordapoptosis-
dc.subject.keywordreactive oxygen species-
dc.citation.volume70-
dc.citation.number6-
dc.citation.startPage849-
dc.citation.endPage857-
dc.identifier.bibliographicCitationJOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, Vol.70(6) : 849-857, 2019-12-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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