RRC ID 39759
著者 Fuji Y, Matsura T, Kai M, Kawasaki H, Yamada K.
タイトル Protection by polaprezinc, an anti-ulcer drug, against indomethacin-induced apoptosis in rat gastric mucosal cells.
ジャーナル Jpn J Pharmacol
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 microM IND in a dose-dependent manner, and 50 microM PZ exhibited the maximum inhibitory effect. Among PZ subcomponents, zinc but not L-carnosine played a pivotal role in this antiapoptotic function. PZ did not affect mitochondrial cytochrome c release upstream of caspase-3 activation in the IND-induced apoptotic signal pathway. Treatment with 500 microM IND evidently produced reactive oxygen species (ROS) in RGM1 cells. However, PZ did not scavenge ROS in IND-treated cells. Moreover, N-acetylL-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.
巻・号 84(1)
ページ 63-70
公開日 2000-9-1
DOI 10.1254/jjp.84.63
PMID 11043455
MeSH Acetylcysteine / pharmacology Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology Anti-Ulcer Agents / pharmacology* Apoptosis* Carnosine / analogs & derivatives* Carnosine / pharmacology* Cells, Cultured Cytochrome c Group / metabolism Dose-Response Relationship, Drug Drug Interactions Enzyme Activation / drug effects Gastric Mucosa / cytology Gastric Mucosa / drug effects* Indomethacin Organometallic Compounds / pharmacology* Peptide Hydrolases / metabolism Protective Agents / pharmacology Rats Rats, Wistar Reactive Oxygen Species / metabolism Time Factors Zinc / metabolism Zinc Compounds Zinc Sulfate / pharmacology
引用数 27
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)