Differential effect of oxidative or excitotoxic stress on the transcriptional profile of amyotrophic lateral sclerosis-linked mutant SOD1 cultured neurons
| Autor: | Joël Lachuer, Nadia Boutahar, Evelyne Reynaud, Jean Philippe Camdessanché, Jean-Christophe Antoine, Anne Wierinckx, François Lassabliere, Jacques Borg |
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| Rok vydání: | 2011 |
| Předmět: |
N-Methylaspartate
Microarray Cell Survival SOD1 Neurotoxins Excitotoxicity Mice Transgenic Biology Protein degradation medicine.disease_cause Statistics Nonparametric Cellular and Molecular Neuroscience Mice Mice Neurologic Mutants Superoxide Dismutase-1 Neurotrophic factors Gene expression medicine Animals Humans Cells Cultured Oligonucleotide Array Sequence Analysis Cerebral Cortex Neurons KIF17 Analysis of Variance Superoxide Dismutase Gene Expression Profiling Amyotrophic Lateral Sclerosis Hydrogen Peroxide Oxidants Molecular biology Cell biology Gene expression profiling Oxidative Stress nervous system Gene Expression Regulation |
| Zdroj: | Journal of neuroscience research. 89(9) |
| ISSN: | 1097-4547 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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