Protective Effect of Supplemental Superoxide Dismutase on Survival of Neuronal Cells During Starvation: Requirement for Cytosolic Distribution
| Autor: | Robert A. Hallewell, Neil F. Fairweather, Jean Lud Cadet, Christopher C. Matthews, Jan B. Wollack, Dayse M. Figueiredo, Paul S. Fishman, Gordon Dougan |
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| Rok vydání: | 2000 |
| Předmět: |
Cell Survival
Green Fluorescent Proteins SOD1 Cell Mice Inbred Strains Mice Transgenic Transfection Gene Expression Regulation Enzymologic Green fluorescent protein Superoxide dismutase Mice Neuroblastoma Cellular and Molecular Neuroscience chemistry.chemical_compound Tetanus Toxin Genes Reporter Tumor Cells Cultured medicine Animals Cellular localization Cerebral Cortex Neurons Cell Death biology Superoxide Dismutase Superoxide General Medicine Fusion protein Molecular biology Peptide Fragments Luminescent Proteins Oxidative Stress medicine.anatomical_structure chemistry Starvation biology.protein Indicators and Reagents Energy Metabolism |
| Zdroj: | Journal of Molecular Neuroscience. 14:155-166 |
| ISSN: | 0895-8696 |
| DOI: | 10.1385/jmn:14:3:155 |
| Popis: | There is evidence that raising cellular levels of Cu2+/Zn2+ superoxide dismutase (SOD1) can protect neurons from oxidative injury. We compared a novel method of elevating neuronal SOD activity using a recombinant hybrid protein composed of the atoxic neuronal binding domain of tetanus toxin (C fragment or TTC) and human SOD1 (hSOD1) with increasing cellular SOD levels through overexpression. Fetal murine cortical neurons or N18-RE-105 cells were incubated with the TTC-hSOD1 hybrid protein and compared to cells constitutively expressing hSOD1 for level of SOD activity, cellular localization of hSOD1, and capacity to survive glucose and pyruvate starvation. Cells incubated with TTC-hSOD1 showed a threefold increase in cellular SOD activity over control cells. This level of increase was comparable to fetal cortical neurons from transgenic mice constitutively expressing hSOD1 and transfected N18-RE-105 cells expressing a green fluorescent protein-hSOD1 fusion protein (GFP-hSOD1). Human SOD1 was distributed diffusely throughout the cytoplasm of the transgenic murine neurons and transfected N18-RE-105 cells. In contrast, cells incubated with TTC-hSOD1 showed hSOD1 localized to the cell surface and intra-cytoplasmic vesicles. The cells expressing hSOD1 showed enhanced survival in glucose- and pyruvate-free medium. Neither cortical neurons nor N18-RE-105 cells incubated in TTC-hSOD1 showed increased survival during starvation. Access to the site where toxic superoxides are generated or their targets may be necessary for the protective function of SOD1. |
| Databáze: | OpenAIRE |
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