Role of NADPH Oxidase and Calcium in Cerulein-Induced Apoptosis: Involvement of Apoptosis-Inducing Factor

Authors: YU, JI HOON1; KIM, KYUNG HWAN1; KIM, HYEYOUNG2

Source: Annals of the New York Academy of Sciences, Volume 1090, Number 1, December 2006 , pp. 292-297(6)

Publisher: Wiley-Blackwell

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Abstract:

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Apoptosis linked to oxidative stress has been implicated in pancreatitis. NADPH oxidase has been considered as a major source of reactive oxygen species (ROS) during inflammation and apoptosis in pancreatic acinar cells. Recently we demonstrated that NADPH oxidase subunits Nox1, p27phox, p47phox, and p67phox are constitutively expressed in pancreatic acinar cells and may contribute to apoptosis in pancreatic acinar AR42J cells stimulated with cerulein. The present study aims to investigate the apoptotic mechanism of pancreatic acinar cells stimulated with cerulein by determining whether cerulein induces apoptosis-inducing factor (AIF) expression and whether cerulein-induced expression of AIF is inhibited by transfection with antisense oligonucleotide (AS ODN) of p47phox or p67phox or treatment with a Ca2+ chelator BAPTA-AM. As a result, cerulein induced the expression of apoptotic gene AIF. Transfection with AS ODN of p47phox or p67phox or treatment with BAPTA-AM inhibited cerulein-induced AIF expression in pancreatic acinar AR42J cells. These results demonstrate that NADPH oxidase and calcium have a role in cerulein-induced apoptosis in pancreatic acinar AR42J cells by inducing the expression of AIF. In conclusion, the increase in intracellular Ca2+ and NADPH oxidase activity may be the upstream event of apoptotic gene (AIF) expression, which contributes to cerulein-induced apoptosis in pancreatic acinar AR42 cells.

Keywords: cerulein; NADPH oxidase; AIF; Ca2+; AR42J cells

Document Type: Research article

DOI: http://dx.doi.org/10.1196/annals.1378.031

Affiliations: 1: Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul 120-752, Korea 2: Department of Food Science and Nutrition, Brain Korea 21 Project, College of Human Ecology, Biomedical Secretion Research Center, Yonsei University, Seoul 120-749, Korea

Publication date: 2006-12-01

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