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SkQ系列线粒体靶向抗氧化剂对红细胞氧化溶血的抑制作用

Inhibition of oxidative hemolysis in erythrocytes by mitochondria-targeted antioxidants of SkQ series.

作者信息

Omarova E O, Antonenko Y N

机构信息

Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow, 119991, Russia.

出版信息

Biochemistry (Mosc). 2014 Feb;79(2):139-45. doi: 10.1134/S0006297914020072.

DOI:10.1134/S0006297914020072
PMID:24794729
Abstract

In the present work we studied the effect of antioxidants of the SkQ1 family (10-(6'-plastoquinonyl)decyltriphenylphosphonium) on the oxidative hemolysis of erythrocytes induced by a lipophilic free radical initiator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) and a water-soluble free radical initiator 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). SkQ1 was found to protect erythrocytes from hemolysis, 2 μM being the optimal concentration. Both the oxidized and reduced SkQ1 forms exhibited protective properties. Both forms of SkQ1 also inhibited lipid peroxidation in erythrocytes induced by the lipophilic free radical initiator AMVN as detected by accumulation of malondialdehyde. However, in the case of induction of erythrocyte oxidation by AAPH, the accumulation of malondialdehyde was not inhibited by SkQ1. In the case of AAPH-induced hemolysis, the rhodamine-containing analog SkQR1 exerted a comparable protective effect at the concentration of 0.2 μM. At higher SkQ1 and SkQR1 concentrations, the protective effect was smaller, which was attributed to the ability of these compounds to facilitate hemolysis in the absence of oxidative stress. We found that plastoquinone in the oxidized form of SkQ1 could be reduced by erythrocytes, which apparently accounted for its protective action. Thus, the protective effect of SkQ in erythrocytes, which lack mitochondria, proceeded at concentrations that are two to three orders of magnitude higher than those that were active in isolated mitochondria.

摘要

在本研究中,我们研究了SkQ1家族的抗氧化剂(10-(6'-质体醌基)癸基三苯基鏻)对由亲脂性自由基引发剂2,2'-偶氮二(2,4-二甲基戊腈)(AMVN)和水溶性自由基引发剂2,2'-偶氮二(2-甲基丙脒)二盐酸盐(AAPH)诱导的红细胞氧化溶血的影响。发现SkQ1可保护红细胞免于溶血,2 μM为最佳浓度。SkQ1的氧化形式和还原形式均表现出保护特性。两种形式的SkQ1还抑制了由亲脂性自由基引发剂AMVN诱导的红细胞脂质过氧化,这可通过丙二醛的积累来检测。然而,在由AAPH诱导红细胞氧化的情况下,SkQ1并未抑制丙二醛的积累。在AAPH诱导溶血的情况下,含罗丹明的类似物SkQR1在0.2 μM的浓度下发挥了相当的保护作用。在更高的SkQ1和SkQR1浓度下,保护作用较小,这归因于这些化合物在无氧化应激时促进溶血的能力。我们发现SkQ1氧化形式中的质体醌可被红细胞还原,这显然解释了其保护作用。因此,SkQ在缺乏线粒体的红细胞中的保护作用在比在分离的线粒体中具有活性的浓度高两到三个数量级的浓度下进行。

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