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Over‐expression of antioxidant enzymes protects cultured hippocampal and cortical neurons from necrotic insults
Author(s) -
Wang Hui,
Cheng Elise,
Brooke Sheila,
Chang Pearl,
Sapolsky Robert
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02123.x
Subject(s) - neurotoxicity , reactive oxygen species , catalase , biochemistry , antioxidant , lipid peroxidation , chemistry , glutathione , hydrogen peroxide , glutathione peroxidase , glutamate receptor , biology , enzyme , microbiology and biotechnology , toxicity , receptor , organic chemistry
There is now considerable knowledge concerning neuron death following necrotic insults, and it is believed that the generation of reactive oxygen species (ROS) and oxidative damage play a pivotal role in the neuron death. Prompted by this, we have generated herpes simplex virus‐1 amplicon vectors over‐expressing the genes for the antioxidant enzymes catalase (CAT) or glutathione peroxidase (GPX), both of which catalyze the degradation of hydrogen peroxide. Over‐expression of each of these genes in primary hippocampal or cortical cultures resulted in increased enzymatic activity of the cognate protein. Moreover, each enzyme potently decreased the neurotoxicity induced by kainic acid, glutamate, sodium cyanide and oxygen/glucose deprivation. Finally, these protective effects were accompanied by parallel decreases in hydrogen peroxide accumulation and the extent of lipid peroxidation. These studies not only underline the key role played by ROS in the neurotoxicity of necrotic insults, but also suggest potential gene therapy approaches.