文章基本信息

标题：Mechanism for the Inhibitory Effect of a Seleno-Organic Compound, Ebselen, and Its Analogues on Superoxide Anion Production in Guinea Pig Polymorphonuclear Leukocytes
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作者：Kyoko WAKAMURA ; Toshiaki OHTSUKA ; Naoki OKAMURA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1990
卷号：13
期号：7
页码：421-425
DOI：10.1248/bpb1978.13.421
出版社：The Pharmaceutical Society of Japan
摘要：Effects of Ebselen and its analogs (PZ-25, NAT06-123, Nat02-761, Nat02-801, NAT06-099, and NAT06-513) on superoxide anion (O^-₂) production induced by tetradecanoyl phorbol acetate (TPA) were examined in intact guinea pig polymorphonuclear leukocytes (PMNL). Four compounds having a structure of 1, 2 benzoisoselenazol-3-(2H) one (Ebselen, NAT06-123, and NAT02-761) and its sulfur-substituted analog (PZ-25), had a potent inhibitory effect on O^-₂ production as compared with others. Ebselen and NAT06-123 also markedly inhibited nicotinamide adenine dinuclestide phosphate (NADPH) oxidase activity, which is responsible for O^-₂ production in intact cells, and in a particulate fraction prepared from TPA-stimulated PMNL, whereas PZ-25 inhibited this enzyme weakly and NAT02-761 did not. On the other hand, Ebselen and PZ-25 had the same degree of potent inhibitory effect on protein kinase C which was involved in the regulation of NADPH oxidase activation. Thus, it is plausible that inhibition of O^-₂ production in intact PMNL by these compounds were due not only to direct inhibition of NADPH oxidase but also to inhibition of protein kinase C.
关键词：protein kinase C