Influence of Mitochondrial ATP-Sensitive Potassium Channels on Toxic Effect of Amyloid-beta 25-35

摘要

Amyloid-beta (A beta) is the main component of senile plaques, one of the hallmarks of Alzheimer(,)s disease. Is been shown that A beta 25-35 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 A beta and the protective effect of BSA, by studying the influence of diazoxide (DIAZ) and tolbutamide (TOLB) on the effect of A beta 25-35 in neuronal morphology, cell viability and ROS generation in presence and absence of BSA. DIAZ decreased ROS generation induced by A beta 25-35 in a concentration dependent manner, but increased with the addition of BSA. TOLB increased A beta 25-35 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 A beta 25-35. Hence, it could be proposed that MitoKATP channels participate on toxic effects of A beta 25-35, but not in protective effect of BSA, which seems to go through an extraneuronal mechanism.