Overexpression of Copper/Zinc Superoxide Dismutase in Transgenic Rats Protects Vulnerable Neurons against Ischemic Damage by Blocking the Mitochondrial Pathway of Caspase Activation

• DOI: 10.1523/jneurosci.22-01-00209.2002
• Publication Date: 2018-04-05T00:15:54Z
• Authors: Taku Sugawara; Nobuo Noshita; Anders Lewén; Yvan Gasche; Michel Ferrand-Drake; Miki Fujimura; Yuiko Morita-Fuji...; Pak H. Chan
• Keywords: SOD2

Mitochondria are known to be involved in the early stage of apoptosis by releasing cytochrome c , caspase-9, and second mitochondria-derived activator caspases (Smac). We have reported that overexpression copper/zinc superoxide dismutase (SOD1) reduced production ameliorated neuronal injury hippocampal CA1 subregion after global ischemia. However, role oxygen free radicals produced ischemia/reperfusion mitochondrial signaling pathway has not been clarified. Five minutes ischemia was induced male SOD1-transgenic (Tg) wild-type (Wt) littermate rats. Cytosolic expression Smac activation were evaluated immunohistochemistry, Western blot, caspase activity assay. Apoptotic cell death characterized DNA nick end single-stranded labeling. In Wt animals, production, release Smac, cleaved caspase-9 observed Active caspase-3 subsequently increased, 85% neurons showed apoptotic damage 3 d Tg animals less release. Subsequent active evident, only 45% damage. A inhibitor ( N- benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone) animals. These results suggest SOD1 oxidative stress, thereby attenuating resulting death. Oxygen may play a pivotal