Cyclosporin A and Bcl-2 do not inhibit quinolinic acid-induced striatal excitotoxicity in rodents

被引：10

作者：

Maciel, EN

Schierle, GSK

Hansson, O

Brundin, P

Castilho, RF ^{[1
]}

机构：

[1] Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, BR-13083970 Campinas, SP, Brazil

[2] Lund Univ, Wallenberg Neurosci Ctr, Sect Neuronal Survival, S-22184 Lund, Sweden

来源：

EXPERIMENTAL NEUROLOGY | 2003年 / 183卷 / 02期

基金：

巴西圣保罗研究基金会;

关键词：

Bcl-2; calcium; cyclosporin A; mitochondrial permeability transition; NMDA; quinolinic acid; striatum;

D O I：

10.1016/S0014-4886(03)00165-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in addition Bcl-2 also inhibits apoptotic stimuli-mediated release of mitochondrial apoptogenic factors. Isolated brain mitochondria from cyclosporin A-treated rats showed resistance to Ca2+-induced dissipation of the membrane potential, indicating protection against MPT. We conclude that quinolinic acid-mediated striatal excitotoxicity is not dependent on MPT and Bcl-2-sensitive apoptotic cell death pathways. (C) 2003 Elsevier Science (USA). All rights reserved.

引用

页码：430 / 437

页数：8

共 59 条

[1] SAFRANINE AS A PROBE OF MITOCHONDRIAL-MEMBRANE POTENTIAL [J].