12 37

Cited 0 times in

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

Authors
 J H Yu  ;  J W Lim  ;  H Kim 
Citation
 JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, Vol.70(6) : 849-857, 2019-12 
Journal Title
JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
ISSN
 0867-5910 
Issue Date
2019-12
MeSH
Acinar Cells / drug effects* ; Acinar Cells / pathology ; Acute Disease ; Animals ; Apoptosis / physiology ; Cell Survival / drug effects ; Cells, Cultured ; Ceruletide ; Gene Expression Regulation ; NADPH Oxidases / metabolism ; NF-kappa B / metabolism ; Oxidative Stress ; Pancreatitis / physiopathology* ; Pancreatitis-Associated Proteins / genetics* ; Rats ; Reactive Oxygen Species / metabolism
Keywords
cerulein ; nicotinamide adenine dinucleotide phosphate oxidase ; nuclear factor-kappa B ; pancreatitis-associated protein-1 ; pancreatic acinar cells ; apoptosis ; reactive oxygen species
Abstract
Pancreatitis 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.
Files in This Item:
T9992019181.pdf Download
DOI
10.26402/jpp.2019.6.04
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189183
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links