Exp Neurobiol.  2010 Sep;19(2):90-96. 10.5607/en.2010.19.2.90.

Etoposide Reduces Peroxynitrite-Induced Cytotoxicity via Direct Scavenging Effect

• Choi IY
• Kim WK

• KMID: 1460705
• DOI: http://doi.org/10.5607/en.2010.19.2.90

Abstract

Previously, we reported that glucose-deprived astrocytes are more vulnerable to the cytotoxicity of peroxynitrite, the reaction product of nitric oxide and superoxide anion. The augmented vulnerability of glucose-deprived astrocytes to peroxynitrite cytotoxicity was dependent on their proliferation rate. Inhibition of cell cycle progression has been shown to inhibit the apoptotic cell death occurring in cerebral ischemia-reperfusion. In the present study, we demonstrate that the increased death of glucose-deprived astrocytes by peroxynitrte was largely blocked by the cell cycle phase G2/M transition blocker etoposide. However, the cytoprotective effect of etoposide was not associated with its inhibition of cell cycle progression. Instead, etoposide effectively scavenged peroxynitrite. However, etoposide did not scavenge individual nitric oxide and superoxide anion and it did not prevent the hydrogen peroxide-induced cytotoxicity. The present results indicate that etoposide prevents the toxicity of peroxynitrite in astrocytes by directly scavenging peroxynitrite, not by inhibiting cell cycle progression.

Keyword

etoposide; peroxynitrite; glucose deprivation; astrocyte; cell death

MeSH Terms

Astrocytes
Cell Cycle
Cell Death
Etoposide
Hydrogen
Nitric Oxide
Peroxynitrous Acid
Superoxides
Etoposide
Hydrogen
Nitric Oxide
Peroxynitrous Acid
Superoxides