Huperzine A protects isolated rat brain mitochondria against β-amyloid peptide

被引：107

作者：

Gao, Xin ^{[1
]}

Zheng, Chun Yan ^{[1
]}

Yang, Ling ^{[1
]}

Tang, Xi Can ^{[1
]}

Zhang, Hai Yan ^{[1
]}

机构：

[1] Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2009年 / 46卷 / 11期

基金：

美国国家科学基金会;

关键词：

Huperzine A; beta-Amyloid peptide; Mitochondria; Oxidative phosphorylation; Free radicals; PERMEABILITY TRANSITION PORE; ALPHA-KETOGLUTARATE DEHYDROGENASE; NATURAL CHOLINESTERASE INHIBITOR; CYTOCHROME-C RELEASE; ALZHEIMERS-DISEASE; LIVER-MITOCHONDRIA; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; FREE-RADICALS; A-BETA;

D O I：

10.1016/j.freeradbiomed.2009.02.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Our previous work in cells and animals showed that mitochondria are involved in the neuroprotective effect of huperzine A (HupA). In this study, the effects of HupA on isolated rat brain mitochondria were investigated. In addition to inhibiting the A beta(25-35) (40 mu M)-induced decrease in mitochondrial respiration, adenosine 5'-triphosphate (ATP) synthesis, enzyme activity, and transmembrane potential, HupA (0.01 or 0.1 mu M) effectively prevented A beta-induced mitochondrial swelling, reactive oxygen species increase, and cytochrome c release. More interestingly, administration of HupA to isolated mitochondria promoted the rate of ATP production and blocked mitochondrial swelling caused by normal osmosis. These results indicate that HupA protects mitochondria against A beta at least in part by preserving membrane integrity and improving energy metabolism. These direct effects on mitochondria further extend the noncholinergic functions of HupA. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：1454 / 1462

页数：9

共 77 条

[1]

Gradual alteration of mitochondrial structure and function by β-amyloids:: Importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release [J].