Miura T, Muraoka S, Fujimoto Y
Hokkaido College of Pharmacy, Otaru, Japan.
J Steroid Biochem Mol Biol. 1998 Oct;67(1):57-62. doi: 10.1016/s0960-0760(98)00068-5.
The effect of estrogens, including estrone (E1), estradiol-17beta (E2), estriol (E3) and 2-hydroxyestradiol (2-OH-E2), on the oxidative damage induced by ferrylmyoglobin (ferrylMb) was investigated. These estrogens inhibited lipid peroxidation induced by ferrylMb. The ability of 2-OH-E2 to inhibit lipid peroxidation was much greater than the other estrogens. Furthermore, 2-OH-E2 trapped 2,2'-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals more rapidly, and among these estrogens only 2-OH-E2 reacted with 2,2-diphenyl-1-picrylhydrazyl. These results suggest that the ability of 2-OH-E2 to inhibit lipid peroxidation is because it scavenges lipid peroxyl and carbon-centered radicals. Estrogens, except for 2-OH-E2, partially prevented the inactivation of alcohol dehydrogenase (ADH) induced by ferrylMb. Of interest, however, the exposure of sulfhydryl (SH) enzymes to ferrylMb in the presence of 2-OH-E2 dramatically increased the inhibition of the enzyme activity. Ascorbic acid (ASA) and reduced glutathione (GSH) strongly inhibited the inactivation of ADH induced by ferrylMb in the presence of 2-OH-E2. During the reaction of ferrylMb with ASA or GSH in the presence of 2-OH-E2, large amounts of oxymyoglobin were formed, suggesting the involvement of the semiquinone from 2-OH-E2 in the reduction of metmyoglobin. Presumably, the semiquinone formed from 2-OH-E2 oxidizes the SH group of enzymes to facilitate the rapid inactivation of the SH enzymes induced by ferrylMb.
研究了包括雌酮（E1）、雌二醇 - 17β（E2）、雌三醇（E3）和2 - 羟基雌二醇（2 - OH - E2）在内的雌激素对高铁肌红蛋白（ferrylMb）诱导的氧化损伤的影响。这些雌激素抑制了ferrylMb诱导的脂质过氧化。2 - OH - E2抑制脂质过氧化的能力远大于其他雌激素。此外，2 - OH - E2能更迅速地捕获2,2'-偶氮双 - （2 - 脒基丙烷） - 二盐酸盐过氧自由基，并且在这些雌激素中只有2 - OH - E2能与2,2 - 二苯基 - 1 - 苦基肼反应。这些结果表明，2 - OH - E2抑制脂质过氧化的能力是因为它能清除脂质过氧自由基和碳中心自由基。除2 - OH - E2外，其他雌激素能部分防止ferrylMb诱导的乙醇脱氢酶（ADH）失活。然而，有趣的是，在2 - OH - E2存在的情况下，巯基（SH）酶暴露于ferrylMb会显著增加酶活性的抑制。在2 - OH - E2存在的情况下，抗坏血酸（ASA）和还原型谷胱甘肽（GSH）强烈抑制ferrylMb诱导的ADH失活。在2 - OH - E2存在的情况下，ferrylMb与ASA或GSH反应时，会形成大量的氧合肌红蛋白，这表明2 - OH - E2的半醌参与了高铁肌红蛋白的还原。据推测，由2 - OH - E2形成的半醌会氧化酶的SH基团，从而促进ferrylMb诱导的SH酶快速失活。
