PMID: 11319773Apr 25, 2001Paper

Role of oxidative stress in the apoptotic cell death of cultured cerebellar granule neurons

Journal of Neuroscience Research
Antonio Valencia, J Morán

Abstract

When cultured cerebellar granule neurons (CGN) are transferred from 25 mM KCl (K25) to 5 mM KCl (K5) caspase-3 and caspase-8, but not caspase-1 or caspase-9,activities are induced and cells die apoptotically. CGN death was triggered by a [Ca(2+)](i) modification when [Ca(2+)](i) was reduced from 300 nM to 50 nM in a K5 medium. The [Ca(2+)](i) changes were followed by an increase in ROS levels. The generation of both cytosolic and mitochondrial reactive oxygen species (ROS) occurred at three different times, 10 min, 30 min and 3--4 hr but only those ROS produced after 3--4 hr are involved in the process of cell death. When CGN cultured in a K5 medium are treated with different antioxidants like scavengers of ROS (mannitol, DMSO) or antioxidant enzymes (superoxide dismutase and catalase) phosphatidylserine translocation, caspase activity, chromatin condensation and cell death is markedly diminished. The protective effect of antioxidants is not mediated through a modification in [Ca(2+)](i). Caspase activation, PS translocation and chromatin condensation were downstream of ROS production. In contrast to H(2)O(2), ROS produced by a xanthine/xanthine oxidase system in CGN cultured in K25 were able to directly induce caspase-3 activa...Continue Reading

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Citations

Apr 15, 2004·Free Radical Biology & Medicine·Antonio Valencia, Julio Morán
Dec 10, 2002·Neurochemistry International·Wen-Pei Tseng, Shoei-Yn Lin-Shiau
Nov 6, 2003·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Rosalba AmodioEnnio Esposito
Aug 3, 2002·Journal of Neurochemistry·Francisco Javier Martín-RomeroCarlos Gutiérrez-Merino
Aug 3, 2002·Journal of Neurochemistry·Francisco Javier Martín-RomeroCarlos Gutiérrez-Merino
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