Dysregulation of Stathmin, a Microtubule-Destabilizing Protein, and Up-Regulation of Hsp25, Hsp27, and the Antioxidant Peroxiredoxin 6 in a Mouse Model of Familial Amyotrophic Lateral Sclerosis
| Autor: | Daniel S. Spellman, Nicholas K. Gonatas, Christoph W. Strey, Xiaosong Wang, John D. Lambris, Anna Stieber, Jacqueline O. Gonatas |
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| Rok vydání: | 2004 |
| Předmět: |
animal diseases
HSP27 Heat-Shock Proteins Golgi Apparatus Microtubules Antioxidants Mass Spectrometry Mice Protein Isoforms Electrophoresis Gel Two-Dimensional Phosphorylation Heat-Shock Proteins Motor Neurons Neurons biology Neurodegenerative Diseases Parkinson Disease Immunohistochemistry Neoplasm Proteins Up-Regulation Original Research Paper Peroxidases Spinal Cord Microtubule Proteins symbols Plasmids Blotting Western SOD1 Mice Transgenic Stathmin Transfection Models Biological Pathology and Forensic Medicine symbols.namesake Hsp27 Microtubule Heat shock protein Animals Humans Immunoprecipitation Phosphatidylinositol transfer protein Amyotrophic Lateral Sclerosis nutritional and metabolic diseases Peroxiredoxins Golgi apparatus Phosphoproteins Molecular biology Protein Structure Tertiary nervous system diseases Gene Expression Regulation Microscopy Fluorescence Astrocytes Mutation biology.protein Peroxiredoxin HeLa Cells Molecular Chaperones Peroxiredoxin VI |
| Zdroj: | The American Journal of Pathology. 165:1701-1718 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)63426-8 |
| Popis: | Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause dominantly inherited familial amyotrophic lateral sclerosis. The identification of differentially regulated proteins in spinal cords of paralyzed mice expressing SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1. Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and phosphorylated isoform, and up-regulation of heat shock proteins 25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha, apolipoprotein E, and ferritin heavy chain. Stathmin accumulated in the cytoplasm of 30% of spinal cord motor neurons with fragmented Golgi apparatus. Overexpression of Stathmin in HeLa cells was associated with collapse of microtubule networks and Golgi fragmentation. These results, together with the decrease of one Stathmin isoform, suggest a role of the protein in Golgi fragmentation. Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons and astrocytes. Mutant SOD1 may thus deprive cells of the anti-apoptotic and other protective activities of Hsp25. Astrocytes contained peroxiredoxin 6, a unique nonredundant antioxidant. The up-regulation of peroxiredoxin 6 probably constitutes a defense to oxidative stress induced by SOD1(G93A). Direct effects of SOD1(G93A) or sequential reactions triggered by the mutant may cause the protein changes. |
| Databáze: | OpenAIRE |
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