title: Differential effect of oxidative or excitotoxic stress on the transcriptional profile of amyotrophic lateral sclerosis-linked mutant SOD1 cultured neurons.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The causes of most cases of ALS are as yet undefined. In a previous study, it was shown that N-methyl-D-aspartate (NMDA) and H(2)O(2) stimuli reduce neuronal survival in cortical neurons in culture (Boutahar et al., 2008). To identify variations in gene expression in response to these neurotoxins in transgenic vs. control cortical neurons cultures, both microarray and RT-PCR analysis were performed. High-density oligonucleotide microarrays showed changes in the expression of about 600 genes involved in protein degradation, neurotrophic factors pathway, cell cycle, inflammation, cytoskeleton, cell adhesion, transcription, or signalling. The most up-regulated genes following H(2)O(2) treatment were involved in cytoskeletal organization and axonal transport, such as ARAP2, KIF17, and DKK2, or in trophic factors pathways, such as insulin-like growth factor-binding protein 4 (IGFBP4), FGF17, and serpin2. The most down-regulated genes were involved in ion transport, such as TRPV1. After NMDA treatment, the most up-regulated genes were involved in protein degradation, such as ubiquitin-conjugating enzyme E2I and cathepsin H, and the most down-regulated genes were involved in ion transport, such as SCN7A. We conclude that these neurotoxins act through different transcriptional inductions, and these changes may reflect an adaptative cellular response to the cellular stress induced by the neurotoxins involved in ALS in the presence of mutant human SOD1.
authors.affiliation: Laboratoire de Neurobiochimie, Université de Lyon, Saint-Etienne, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutahar
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Camdessanche
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Antoine
authors.forename: Evelyne
authors.initials: E
authors.lastname: Reynaud
authors.forename: François
authors.initials: F
authors.lastname: Lassabliere
authors.forename: Joël
authors.initials: J
authors.lastname: Lachuer
authors.forename: Jacques
authors.initials: J
authors.lastname: Borg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D009498:Neurotoxins; D016877:Oxidants; C000606290:SOD1 protein, human; D016202:N-Methylaspartate; D006861:Hydrogen Peroxide; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1