Gene Therapy in the Nervous System with Superoxide Dismutase.
From: Dept. of Biological Sciences, Stanford University, Gilbert Lab, MC 5020, Stanford, CA 94305-5020, USA.
Brain research
- Publish Date: May 2006
- ISSN: 0006-8993
- Volume: 1088
- Issue: 1
- Pages: 12-8
- Medium: Print
- Language: English
- Citation (JAMA): Zemlyak Ilona, Nimon Vitaliy, Brooke Sheila, et al. Gene Therapy in the Nervous System with Superoxide Dismutase.. Brain Res. May 2006;1088:12-8
Abstract
Neuronal death following necrotic insults involves the generation of reactive oxygen species (ROS). We investigated the effects of antioxidant gene therapy on ROS accumulation after exposure to either sodium cyanide, kainic acid or oxygen glucose deprivation (OGD). Specifically, we generated herpes simplex virus-1 amplicon vector expressing the gene for the antioxidant enzyme CuZnSOD. Overexpression of this gene in primary hippocampal cultures resulted in increased enzymatic activity of the corresponding protein. CuZnSOD significantly protected hippocampal neurons against sodium cyanide insult and the subsequent lipid peroxidation. However, it did not protect against OGD- or kainic-acid-induced toxicity. Moreover, CuZnSOD significantly worsened the toxicity, hydrogen peroxide accumulation and lipid peroxidation induced by kainic acid. As a possible explanation for this surprising worsening, CuZnSOD overexpression increased glutathione peroxidase activity in the presence of sodium cyanide but had no effect on catalase or glutathione peroxidase activity in the presence of kainic acid. Thus, cells were unlikely to be able to detoxify the excess hydrogen peroxide produced as a result of the CuZnSOD overexpression. These studies can be viewed as a cautionary note concerning gene therapy intervention against necrotic insults.
Mesh Headings (Keywords): Animals, Cells, Cultured, Cyanates, Embryo, Mammalian, Free Radical Scavengers, Gene Therapy, Genetic Vectors, Hippocampus, Hydrogen Peroxide, Kainic Acid, Lipid Peroxides, Nervous System, Neurons, Neurotoxins, Rats, Superoxide Dismutase, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16630587
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