@misc{oai:repo.qst.go.jp:00067650,
 author = {Nakagawa, Hidehiko and Komai, Nobuko and Takusagawa, Mitsuko and Ozawa, Toshihiko and Ikota, Nobuo and 中川 秀彦 and 駒井 信子 and 田草川 光子 and 小澤 俊彦 and 伊古田 暢夫},
 month = {Nov},
 note = {Reactive nitrogen species, like reactive oxygen species, are potent oxidative stress inducers, and it is suggested that they are involved in various kinds of neurodegenerative diseases. Peroxynitrite (PN) is one of the typical reactive nitrogen species. It can inhibit the mitochondrial electron transfer reaction, and induce cell death in various types of cells. Recently, we found that continuous or repetitive insults of PN on C6 glioma cells resulted in caspase-independent cell death although cytochrome c release was observed. In this paper, we focused on the chemical reactivity of PN on the protein residues, and examined the involvement of PN-induced chemical modification on cytochrome c in the caspase inactivation. The viability of C6 cells was decreased by the treatment of SIN-1, continuous PN generator, in a dose-dependent manner. The activation of caspase-3 and the fragmentation of poly-(ADP-ribose) polymerase were not observed although cytochrome c was released into the cytosol. It was found that cytochrome c was nitrated in C6 cells under the same condition. Using the cell-free caspase activation assay, it was demonstrated that the preparation of cytochrome c treated with synthetic peroxynitrite in vitro lost the activity for the caspase cascade. This functional change of cytochrome c was suppressed by peroxynitrite scavenger, 5-methoxytryptamine. Mass spectrometric analysis revealed that cytochrome c was nitrated and oxidized at the specific amino acid residues. From these results, it was found that PN induced the nitrating and oxidative modification on cytochrome c at the specific residues, and those modifications were suggested to be involved in the cytochrome c inactivation for the caspase cascade., SfN Meeting 2003},
 title = {PEROXYNITRITE-INDUCED OXIDATIVE MODIFICATION ON CYTOCHROME C RELATING TO CASPASE-CASCADE INACTIVATION},
 year = {2003}
}