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水溶性多元醇-甲烷富勒烯作为线粒体靶向抗氧化剂:作用机制

Water-soluble polyol-methanofullerenes as mitochondria-targeted antioxidants: Mechanism of action.

作者信息

Kalacheva Natalia V, Tarasova Gulzada R, Fazleeva Guzel M, Gubskaya Valentina P, Gumerova Dilara R, Rizvanov Albert A, Cherepnev Georgi V

机构信息

Kazan Federal University, Kremlevskaya Str. 18, 420008 Kazan, Russian Federation.

Kazan Federal University, Kremlevskaya Str. 18, 420008 Kazan, Russian Federation.

出版信息

Bioorg Med Chem Lett. 2018 Apr 1;28(6):1097-1100. doi: 10.1016/j.bmcl.2018.02.009. Epub 2018 Feb 8.

DOI:10.1016/j.bmcl.2018.02.009
PMID:29459208
Abstract

The mechanism of an antioxidant action of water-soluble polyol - methanofullerenes C[CHO(OH)] and C[CHO(OH)] as the mild uncouplers of an oxidative phosphorylation and respiration is postulated. According to this mechanism, hydroxyl group of methanofullerenols can be protonated under excess of protons in the intermembrane space of hyperpolarized mitochondria. Protonation of fullerene derivatives is confirmed by the decrease in their negative Zeta potential in the pH below 5.4. Heavily protonated methanofullerenols become positively charged and move into the mitochondrial matrix. As a consequence, the proton gradient is dissipated, which causes a decrease in mitochondrial transmembrane potential (ΔΨ) and reduction in ROS production.

摘要

假定水溶性多元醇 - 甲烷富勒烯C[CHO(OH)]和C[CHO(OH)]作为氧化磷酸化和呼吸作用的温和解偶联剂具有抗氧化作用的机制。根据该机制,在超极化线粒体的膜间空间中质子过量的情况下,甲烷富勒醇的羟基可被质子化。富勒烯衍生物的质子化通过其在pH低于5.4时负Zeta电位的降低得到证实。高度质子化的甲烷富勒醇带正电荷并进入线粒体基质。结果,质子梯度消散,导致线粒体跨膜电位(ΔΨ)降低和活性氧生成减少。

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