Epo protects SOD2-deficient mouse astrocytes from damage by oxidative stress

초록

Erythropoietin (Epo) expression, which regulates erythropoiesis, has been shown in rat and mouse brain after hypoxia. A previous study from our laboratory showed that astrocytes from manganese-superoxide dismutase (SOD2) homozygous knockout (SOD2(-/-)) mice can survive under 5% O-2, but not under normal aerobic conditions. However, the mechanism involved is not clear. Our preliminary study using reverse transcriptase-polymerase chain reaction showed increased Epo mRNA expression in astrocytes cultured with 5% hypoxia compared with astrocytes under normal conditions. After administration of anti-sense Epo, protection decreased with time. Dose-dependent administration of Epo to SOD2(-/-) mouse astrocytes improved their survivability under normal conditions. Survivability of heterozygous SOD2(-/+) mutant and wild-type mouse astrocyte cultures was the same under normal conditions but, after administration of 2 mM of paraquat, a reactive oxygen species generator, survivability of the SOD2(-/+) astrocytes decreased remarkably compared with the wild-type cells. Epo administration 24 h before exposure to paraquat significantly improved the survivability of the SOD2(-/+) astrocytes. Western blot studies suggest that Jak-Stat signal transduction pathways are involved in this process. Our study demonstrates an important ro