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

Hoon Yu Ji, Weon Lim Joo, Hwan Kim Kyung, Tomohiro Morio, Hyeyoung Kim

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68 Citations (Scopus)

Abstract

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 p47phox and p67phox 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 p22phox and p47phox inhibited cerulein-induced ROS production, translocation of NADPH oxidase cytosolic subunits p47phox and p67phox 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.

Original languageEnglish
Pages (from-to)590-602
Number of pages13
JournalFree Radical Biology and Medicine
Volume39
Issue number5
DOIs
Publication statusPublished - 2005 Sep 1

Bibliographical note

Funding Information:
This study was supported by the Korea Research Foundation Grant (KRF-2004-042-E00026).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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