Bcl-2 expression using retrograde transport of adenoviral vectors inhibits cytochrome c-release and caspase-1 activation in motor neurons of mutant superoxide dismutase 1 (G93A) transgenic mice
| Autor: | Shinsuke Kato, Haruo Okado, Eisaku Ohama, Shuji Mita, Satoshi Yamashita, Makoto Uchino |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Genetic Vectors Glycine Cell Count Cytochrome c Group Mice Transgenic Axonal Transport Adenoviridae Superoxide dismutase Mice Mice Neurologic Mutants Viral Proteins Superoxide Dismutase-1 Gene expression medicine Animals Humans Cellular localization Caspase Motor Neurons Alanine Integrases biology Superoxide Dismutase General Neuroscience Cytochrome c Caspase 1 Gene Transfer Techniques Motor neuron Immunohistochemistry Molecular biology Enzyme Activation medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Mutation biology.protein Immunostaining Brain Stem |
| Zdroj: | Neuroscience Letters. 350:17-20 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/s0304-3940(03)00817-6 |
| Popis: | We explored a possible mechanism of the neuro-protective effects of exogenous human Bcl-2 expression on motor neurons of transgenic mice expressing human Cu/Zn superoxide dismutase with a G93A mutation (G93A mice), using retrograde transport and a Cre-loxP recombination system employing adenoviral vectors. We examined the cellular localization of cytochrome c and caspase-1 using immunohistochemical study, in motor neurons of hypoglossal nuclei of G93A mice at 15 weeks after inoculation with the adenoviral vectors, at which time over-expressed exogenous Bcl-2 declined to reach the baseline of intrinsic Bcl-2. We found that a significant number of neurons showed more faint and punctate immunostaining against cytochrome c and significantly less neurons showed immunoreactivity against activated caspase-1, compared with those of mice without inoculation. These results suggest that transient exogenous Bcl-2 expression at the early stage of the disease protects against motor neuronal degeneration in G93A mice by retarding translocation of cytochrome c into the cytosol, and regulating caspase-1 for a substantial period. |
| Databáze: | OpenAIRE |
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