Yasuyoshi Fujii1,2, Tatsuya Matsura1,*, Masachika
Kai1, Hironaka Kawasaki2 and Kazuo Yamada1
1Departmentﾊof Biochemistry and 2Second Department
of Internal Medicine, Faculty of Medicine, Tottori University,
86 Nishi-cho, Yonago 683-8503, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: Polaprezinc [N-(3-aminopropionyl)-L-histidinato
zinc] (PZ), an anti-ulcer drug, is a chelate compound consisting of zinc
and L-carnosine. PZ has been shown to prevent gastric
mucosal injury. In the present study, we investigated the inhibitory effect
of PZ on indomethacin (IND)-induced apoptosis in a rat gastric mucosal cell
line, RGM1. Pretreatment with PZ suppressed caspase-3 activation and subsequent
apoptosis in the cells exposed to 500ﾊmM IND
in a dose-dependent manner, and 50ﾊmM PZ exhibited
the maximum inhibitory effect. Among PZ subcomponents, zinc but not L-carnosine played a pivotal role in this anti-apoptotic
function. PZ did not affect mitochondrial cytochrome c release upstream
of caspase-3 activation in the IND-induced apoptotic signal pathway. Treatment
with 500ﾊmM IND evidently produced reactive oxygen
species (ROS) in RGM1 cells. However, PZ did not scavenge ROS in IND-treated
cells. Moreover, N-acetyl-L-cysteine, a potent
antioxidant, inhibited ROS generation but did not suppress apoptosis in
RGM1 cells exposed to IND. These observations demonstrate a novel pharmacological
action of PZ; i.e., that PZ, and in particular its zinc subcomponent, inhibits
apoptosis via inhibition of caspase-3 activation but not antioxidant activity.
Keywords: Polaprezinc, Indomethacin, Apoptosis, Caspase-3, Reactive oxygen
species
Copyrightｩ The Japanese Pharmacological Society 2000
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