Articles

  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2010; 19(2): 90-96

Published online September 30, 2010

https://doi.org/10.5607/en.2010.19.2.90

© The Korean Society for Brain and Neural Sciences

Etoposide Reduces Peroxynitrite-Induced Cytotoxicity via Direct Scavenging Effect

In-Young Choi and Won-Ki Kim*

Department of Neuroscience, Korea University College of Medicine, Seoul 136-705, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-920-6094, FAX: 82-2-953-6095
e-mail: wonki@korea.ac.kr

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.

Keywords: etoposide, peroxynitrite, glucose deprivation, astrocyte, cell death