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Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam
- Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam
- Choi Y.; Jin Y.; Nam W.; Kim H.-C.; Kim W.-K.
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- Neuroscience Research
- vol. 45, no. 2, pp. 157 - 161
- SCI; SCIE; SCOPUS
- Under glucose-deprived conditions, astrocytes rapidly underwent death due to their increased susceptibility to endogenously produced peroxynitrite (Gila 31, 155-164; J. Neuroimmunol. 112, 55-62; J. Neurochem. 74, 1989-1998). In the present study, the cell membrane-permeable synthetic superoxide dismutase (SOD) mimetic cyclam manganese(III) 1,4,8,11-tetraazacyclodecane (Mn(III)-cyclam) completely inhibited the death of glucose-deprived immunostimulated astrocytes. However, the structurally related compounds Ni(II)-cyclam, Co(II)-cyclam, and H 2-cyclam, which lacks metals, had no or a little cytoprotective effect. Of the cyclams used in this study, only Mn(III)-cyclam completely scavenged the peroxynitrite produced in glucose-deprived immunostimulated astrocytes and significantly blocked the depolarization of mitochondrial transmembrane potential in those cells. The present results suggest that cell membrane-permeable synthetic SOD mimetics such as Mn(III)-cyclam may be potential therapeutic agents for various diseases associated with the endogenous production of peroxynitrite. © 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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