Activation of the peroxisome proliferator-activated receptor-alpha enhances cell death in cultured cerebellar granule cells

Smith, SA, May, FJ, Monteith, GR and Roberts-Thomson, SJ (2001) Activation of the peroxisome proliferator-activated receptor-alpha enhances cell death in cultured cerebellar granule cells. Journal of Neuroscience Research, 66 2: 236-241.


Author Smith, SA
May, FJ
Monteith, GR
Roberts-Thomson, SJ
Title Activation of the peroxisome proliferator-activated receptor-alpha enhances cell death in cultured cerebellar granule cells
Journal name Journal of Neuroscience Research   Check publisher's open access policy
ISSN 0360-4012
Publication date 2001
Sub-type Article (original research)
DOI 10.1002/jnr.1216
Volume 66
Issue 2
Start page 236
End page 241
Total pages 6
Editor J. de Vellis
Place of publication New York
Publisher Wiley-Liss
Collection year 2001
Language eng
Subject C1
320504 Toxicology (incl. Clinical Toxicology)
780105 Biological sciences
Abstract Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a member of the steroid hormone receptor superfamily. In rodents, PPAR alpha. alters genes involved in cell cycle regulation in hepatocytes. Some of these genes are implicated in neuronal cell death. Therefore, in this study, we examined the toxicological consequence of PPAR alpha activation in rat primary cultures of cerebellar granule neurons. Our studies demonstrated the presence of PPAR alpha mRNA in cultures by reverse transcriptase-polymerase chain reaction. After 10 days in vitro, cerebellar granule neuron cultures were incubated with the selective PPAR alpha activator 4-chloro-6-(2,3-xylidino)2-pyrimidinylthioacetic acid (Wy-14,643). The inherent toxicity of Wy-14,643 and the effect of PPAR alpha activation following toxic stimuli were assessed. In these studies, neurotoxicity was induced through reduction of extracellular [KCl] from 25 mM to 5.36 mM. We observed no inherent toxicity of Wy-1 4,643 (24 hr) in cultured cerebellar granule cells. However, after reduction of [KCl], cerebellar granule cell cultures incubated with Wy-14,643 showed significantly greater toxicity than controls. These results suggest a posssible role for PPAR(x in augmentation of cerebellar granule neuronal death after toxic stimuli. (C) 2001 Wiley-Liss, Inc.
Keyword Neurosciences
Neurotoxicity
Ppar
Neuronal Cell Culture
Cerebellar Granule Neurons
Retinoid-x-receptor
Kainate-induced Apoptosis
Nitric-oxide Synthase
Nervous-system
Fatty-acids
Mouse-liver
Ppar-alpha
Rat
Neurons
Gamma
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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