Referenced in: none

Automatically associated channels: Kv10.1

Title: Diazoxide and cyclosporin A protect primary cholinergic neurons against beta-amyloid (1-42)-induced cytotoxicity.

Authors: Xianwei Zeng, Tony Wang, Liangliang Jiang, Guozhao Ma, Shuhui Tan, Jialong Li, Jianxin Gao, Kejing Liu, Yong Zhang

Journal, date & volume: Neurol. Res., 2013 Jun , 35, 529-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23595141

Abstract
Activation of mitochondrial (MitoKATP) channels was found to protect against anoxic and chemical stress in brain. This present study sought to investigate the ability of diazoxide and cyclosporin A to antagonize cytotoxicity induced by beta-amyloid peptide (A-beta1-42) in cultured rat primary basal forebrain cholinergic neurons.Cytotoxicity was induced by A-beta1-42 (2 μM) in the presence of either diazoxide (500 μM), a selective opener of the mitochondrial ATP-sensitive potassium channel (MitoKATP), or cyclosporin A (20 μM), an inhibitor of the mitochondrial permeability transition pore (MTP), or the combination of both the reagents. We determined cell morphology and cell viability using MTT assay and expression levels of anti-apoptotic protein (Bcl-2), pro-apoptotic proteins (Bax, cytochrome C, caspase-3 and cleaved caspase-3) using Western blotting at 24 hours and 72 hours.Cell viability decreased markedly after exposure to A-beta1-42 for 72 hours with a decrease in the expression of Bcl-2 protein and cytochrome C and an increase in the caspase-3 and cleaved caspase-3 levels. Both diazoxide and cyclosporin A exerted significant protective effects on cell viability by ameliorating the decrease in Bcl-2 and the increase in cytochrome c and caspase-3 activity induced by A-beta1-42. The combination of both the reagents had a greater protective effect than either one alone.The present research demonstrates that activation of MitoKATP channels independently or in combination with inhibitors of the MTP can elicit a protective effect against primary cholinergic neuron cytotoxicity induced by A-beta1-42. These findings suggest new mitochondrial targets for the development of therapeutic agents against A-beta-induced cytotoxicity.