NADPH oxidase and apoptosis in cerulein-stimulated pancreatic acinar AR42J cells

被引:70
|
作者
Yu, JH
Lim, JW
Kim, KH
Morio, T
Kim, H [1 ]
机构
[1] Yonsei Univ, Coll Med, Brain KoreaProject Med Sci 21, Dept Pharmacol, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Inst Gastroenterol, Seoul 120752, South Korea
[3] Tokyo Med & Dent Univ, Grad Sch, Dept Pediat & Dev Biol, Tokyo 1138519, Japan
[4] Tokyo Med & Dent Univ, Ctr Cell Therapy, Tokyo 1138519, Japan
基金
新加坡国家研究基金会;
关键词
NADPH oxidase; apoptosis; reactive oxygen species; pancreatic acinar cells;
D O I
10.1016/j.freeradbiomed.2005.04.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Apoptosis linked to oxidative stress has been implicated in pancreatitis. We investigated whether NADPH oxidase mediates apoptosis in cerulein-stimulated pancreatic acinar AR42J cells. We report here that cerulein treatment resulted in the activation of NADPH oxidase, as determined by ROS production, translocation of cytosolic subunits p47(phox) and p67(phox) to the membrane, and interaction between NADPH oxidase subunits. Cerulein induced Ca2+ oscillation, the expression of apoptotic genes p53 and bax, and apoptotic indices (DNA fragmentation, TUNEL staining, caspase 3 activity, decrease in cell viability) in AR42J cells. Treatment with a Ca2+ chelator, BAPTA-AM, or transfection with antisense oligonucleotides for NADPH oxidase subunits p22(phox) and p47(phox) inhibited cerulein-induced ROS production, translocation of NADPH oxidase cytosolic subunits p47(phox) and p67(Phox) to the membrane, and the expression of apoptotic genes and apoptotic indices, as compared to the cells without treatment and those transfected with the corresponding sense oligonucleotides. These results indicate that NADPH oxidase may mediate ROS-induced apoptosis in pancreatic acinar cells in a Ca2+ -dependent manner. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:590 / 602
页数:13
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