Epo protects SOD2‐deficient mouse astrocytes from damage by oxidative stress
- 15 November 2005
- Vol. 53 (4), 360-365
- https://doi.org/10.1002/glia.20289
Abstract
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% O2, 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 role for Epo in the protection of astrocytes from reactive oxygen species. We suggest that Epo can compensate in part for the antioxidant properties of mitochondrial SOD2 deficiency.Keywords
This publication has 24 references indexed in Scilit:
- Neuroprotection by Hypoxic Preconditioning Involves Oxidative Stress-Mediated Expression of Hypoxia-Inducible Factor and ErythropoietinStroke, 2005
- Hypoxia-Induced Stroke Tolerance in the Mouse Is Mediated by ErythropoietinStroke, 2003
- Prolonged hypoxia during cell development protects mature manganese superoxide dismutase‐deficient astrocytes from damage by oxidative stressThe FASEB Journal, 2001
- Manganese superoxide dismutase in diseaseFree Radical Research, 2001
- Detection of erythropoietin in human liquor: Intrinsic erythropoietin production in the brainKidney International, 1997
- Lipid Peroxidation and Antioxidant Activity in Chronic Haemodialysis Patients Treated with Recombinant Human ErythropoietinScandinavian Journal of Urology and Nephrology, 1997
- Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutaseNature Genetics, 1995
- Antioxidant characterizationBiochemical Pharmacology, 1995
- Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proceedings of the National Academy of Sciences, 1990
- Hypoxia-Induced Dysfunctions and Injury of Astrocytes in Primary Cell CulturesJournal of Cerebral Blood Flow & Metabolism, 1989