Abstract

Amyloid-β (Aβ) is the main component of senile plaques, one of the hallmarks of Alzheimer^,s disease. Is been shown that Aβ25–35 decreased neuronal viability while it increased generation of reactive oxygen species (ROS), and albumin (BSA) prevented ROS production and neuronal death in a dose-and time-dependent manner. One of the major sources of ROS is mitochondrion, and is believed that Mitochondrial ATP-regulated potassium channels (mitoKATP) protect synapses and neurons against oxidative and metabolic stress by modulating inner membrane potential and ROS production. Here we investigate the possible participation of MitoKATP channels on toxic effect of Aβ and the protective effect of BSA, by studying the influence of diazoxide (DIAZ) and tolbutamide (TOLB) on the effect of Aβ25–35 in neuronal morphology, cell viability and ROS generation in presence and absence of BSA. DIAZ decreased ROS generation induced by Aβ25–35 in a concentration dependent manner, but increased with the addition of BSA. TOLB increased Aβ25–35 effect on ROS production in a concentration dependent manner, but only in presence of BSA. Neither DIAZ nor TOLB rescued neurons from morphological damage and cell death induced by Aβ25–35. Hence, it could be proposed that MitoKATP channels participate on toxic effects of Aβ25–35, but not in protective effect of BSA, which seems to go through an extraneuronal mechanism.

中文翻译：

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线粒体ATP敏感性钾通道对β-淀粉样蛋白25-35毒性作用的影响

摘要

淀粉样蛋白（Aβ）是老年斑的主要成分，是老年痴呆症的标志之一^，的疾病。研究表明，Aβ25-35降低了神经元的活力，同时增加了活性氧（ROS）的生成，而白蛋白（BSA）则以剂量和时间依赖性的方式阻止了ROS的产生和神经元的死亡。ROS的主要来源之一是线粒体，据信线粒体ATP调节的钾通道（mitoKATP）通过调节内膜电位和ROS的产生来保护突触和神经元免受氧化和代谢压力。在这里，我们通过研究重氮（DIAZ）和甲苯磺丁酰胺（TOLB）对Aβ25-35对神经元形态，细胞活力和ROS的影响，研究了MitoKATP通道可能参与Aβ的毒性作用和BSA的保护作用。在存在和不存在BSA的情况下生成。DIAZ以浓度依赖的方式减少了Aβ25-35诱导的ROS生成，但随着BSA的添加而增加。TOLB以浓度依赖的方式（但仅在存在BSA的情况下）增加Aβ25-35对ROS产生的影响。DIAZ和TOLB都无法挽救神经元免受Aβ25-35诱导的形态学损伤和细胞死亡。因此，可以提出MitoKATP通道参与Aβ25-35的毒性作用，但不参与BSA的保护作用，而BSA似乎是通过神经外机制参与的。