Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 77
Diphenyleneiodonium inhibits cerulein-induced apoptosis in pancreatic acinar cells
Ji Hoon Yu, Joo Weon Lim, Kyung Hwan Kim, and Hyeyoung Kim*
Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei
University, College of Medicine, Seoul 120-752, Korea. E-mail: jihoonyu@hotmail.com
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. Diphenyleneiodonium (DPI) is widely used
as an inhibitor of flavoenzymes, particularly NADPH oxidase. We investigated whether
inhibition of NADPH oxidase with treatment of DPI suppresses ROS production and the
activation of NADPH oxidase in pancreatic acinar AR42J cells stimulated with cerulein, and
whether cerulien induces the expression of apoptosis-inducing factor (AIF), caspase-3
activation and apoptosis, which is inhibited by DPI. To determine the effect of DPI on
cerulein-evoked Ca++ influx, intracellular Ca2++ level was monitored in the cells treated
with or without DPI and cultured in the presence of cerulein. As a result, cerulein induced the
activation of NADPH oxidase, determined by ROS production and translocation of cytosolic
subunits p47phox and p67phox to the membrane, which is in parallel with increase in
apoptotic indices, including the expression of AIF, caspase-3 activation, TUNEL staining,
DNA fragmentation and decrease in cell viability. Treatment with DPI inhibited ceruleininduced
activation of NADPH oxidase and apoptosis, but not Ca++ influx in pancreatic acinar
cells. These results demonstrate that inhibition of NADPH oxidase by DPI may alleviate
ROS-mediated apoptosis in pancreatic acinar cells.
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