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过氧化麦角甾醇,一种能选择性增强亚油酸对DNA聚合酶β抑制作用的天然产物。

An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta.

作者信息

Mizushina Y, Watanabe I, Togashi H, Hanashima L, Takemura M, Ohta K, Sugawara F, Koshino H, Esumi Y, Uzawa J, Matsukage A, Yoshida S, Sakaguchi K

机构信息

Department of Applied Biological Science, Science University of Tokyo, Chiba, Japan.

出版信息

Biol Pharm Bull. 1998 May;21(5):444-8. doi: 10.1248/bpb.21.444.

DOI:10.1248/bpb.21.444
PMID:9635497
Abstract

As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M., Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the activities of mammalian DNA polymerases. We found a natural product from a basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy-5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta). However, when EPO at 0.25 mM was present, 10 microM or less of LA almost completely inhibited the pol. beta activity, while almost complete inhibition by LA itself was achieved at 80 microM or higher. Interestingly, under the same conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of the EPO was discussed.

摘要

如前所述(水嶋洋一、田中直、八木浩、黑泽哲、小野上美、瀬戸浩、堀江彻、青柳直、山冈正、松影昭、吉田秀、坂口健,《生物化学与生物物理学学报》,1308 卷,256 - 262 页,1996 年),亚油酸(LA)可抑制哺乳动物 DNA 聚合酶的活性。我们从担子菌灵芝中发现了一种天然产物,它以一种特殊方式增强了 LA 的这种作用。通过光谱分析确定其结构为过氧化麦角甾醇,即 5,8 - 环氧 - 5α,8α - 麦角甾 - 6,22E - 二烯 - 3β - 醇。过氧化麦角甾醇(EPO)本身几乎不抑制小牛胸腺 DNA 聚合酶α(pol.α)或大鼠 DNA 聚合酶β(pol.β)的活性。然而,当存在 0.25 mM 的 EPO 时,10 μM 及以下的 LA 几乎完全抑制了 pol.β的活性,而 LA 本身在 80 μM 及以上时才几乎完全抑制其活性。有趣的是,在相同条件下,EPO 并不影响 LA 对 pol.α的作用。本文讨论了 EPO 的作用模式。

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