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Diphenyleneiodonium suppresses apoptosis in cerulein-stimulated pancreatic acinar cells

Authors
 Ji Hoon Yu  ;  Kyung Hwan Kim  ;  Hyeyoung Kim  ;  Dong Goo Kim 
Citation
 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol.39(11) : 2063-2075, 2007 
Journal Title
 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 
ISSN
 1357-2725 
Issue Date
2007
MeSH
Animals ; Apoptosis/drug effects* ; Apoptosis Inducing Factor/genetics ; Apoptosis Inducing Factor/metabolism ; Calcium/metabolism ; Caspase 3/metabolism ; Cell Line ; Cell Survival/drug effects ; Ceruletide/pharmacology* ; DNA Fragmentation/drug effects ; Enzyme Activation/drug effects ; Gene Expression Regulation/drug effects ; Glutathione/pharmacology ; In Situ Nick-End Labeling ; L-Lactate Dehydrogenase/metabolism ; NADPH Oxidases/metabolism ; Onium Compounds/pharmacology* ; Pancreas, Exocrine/cytology* ; Pancreas, Exocrine/drug effects* ; Pancreas, Exocrine/enzymology ; Pancreas, Exocrine/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/pharmacology
Abstract
NADPH oxidase has been considered a major source of reactive oxygen species in phagocytic and non-phagocytic cells. Apoptosis linked to oxidative stress has been implicated in pancreatitis. Recently, we demonstrated that NADPH oxidase subunits Nox1, p27phox, p47phox, and p67phox are constitutively expressed in pancreatic acinar cells, which are activated by cerulein, a cholecystokinin analogue. Cerulein induces an acute and edematous form of pancreatitis. We investigated whether inhibition of NADPH oxidase by diphenyleneiodonium suppresses the production of reactive oxygen species and apoptosis by determining viable cell numbers, DNA fragmentation, TUNEL staining, caspase-3 activity, and the expression of apoptosis-inducing factor in pancreatic acinar AR42J cells stimulated with cerulein. Inhibition on NADPH oxidase by diphenyleneiodonium was assessed by the alterations in NADPH oxidase activity and translocation of the cytosolic subunits p67phox and p47phox to the membrane. Intracellular Ca2+ level was monitored to investigate the relationship between NADPH oxidase and Ca2+ in cells stimulated with cerulein. As a result, cerulein induced the activation of NADPH, increased production of reactive oxygen species, and apoptotic indices determined by the expression of apoptosis-inducing factor, caspase-3 activation, TUNEL staining, DNA fragmentation, and cell viability. Treatment with DPI inhibited cerulein-induced activation of NADPH oxidase, the production of reactive oxygen species, and apoptosis, but not the increase of intracellular Ca2+ levels in pancreatic acinar cells. These results demonstrate that the cerulein-induced increase in intracellular Ca2+ level may be an upstream event of NADPH oxidase activation. Diphenyleneiodonium, an NADPH oxidase inhibitor, inhibits the expression of apoptosis-inducing factor and caspase-3 activation, and thus apoptosis in pancreatic acinar cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S135727250700177X
DOI
10.1016/j.biocel.2007.05.021
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Dong Goo(김동구)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96132
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