Gene therapy in the nervous system with superoxide dismutase

Brain Research
Ilona ZemlyakR M Sapolsky

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...Continue Reading

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Citations

Mar 19, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Shinichi UsuiPeter A Campochiaro
Feb 23, 2011·International Journal of Molecular Sciences·Supatra AreekitKosum Chansiri
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Aug 11, 2010·Free Radical Biology & Medicine·José M MatésJavier Márquez

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