ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Exposure of cerebellar granule cells (CGCs) to 1-methyl-4-phenylpyridinium (MPP+) results in apoptotic cell death, which is markedly attenuated by co-treatment of CGCs with the radical scavenger vitamin E. Analysis of free radical production and mitochondrial transmembrane potential (ΔΨm), using specific fluorescent probes, showed that MPP+ mediates early radical oxygen species (ROS) production without a loss of ΔΨm. Exposure to MPP+ also produces an early increase in Bad dephosphorylation and translocation of Bax to the mitochondria. These events are accompanied by cytochrome c release from mitochondria to cytosol, which is followed by caspase 3 activation. Exposure of the neurons to vitamin E maintains Bad phosphorylation and attenuates Bax translocation, inhibiting cytochrome c release and caspase activation. MPP+-mediated cytochrome c release is also prevented by allopurinol, suggesting the participation of xanthine oxidase in the process. Our results indicate that free radicals play an active role in the MPP+-induced early events that culminate with cell death.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2003.01520.x
