Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1909825 | Free Radical Biology and Medicine | 2009 | 8 Pages |
Abstract
Nitric oxide (NO) is a major factor contributing to the loss of neurons in ischemic stroke, demyelinating diseases, and other neurodegenerative disorders. NO not only functions as a direct neurotoxin, but also combines with superoxide (O2â) by a diffusion-controlled reaction to form peroxynitrite (ONOOâ), a species that contributes to oxidative signaling and cellular apoptosis. However, the mechanism by which ONOOâ induces apoptosis remains unclear, although subsequent formation of reactive oxygen species (ROS) has been suggested. The aim of this study was to further investigate the triggers of the apoptotic pathway using O2â scavenging with light irradiation to block ONOOâ production. Antiapoptotic effects of light irradiation in sodium nitroprusside (SNP)-treated SH-SY5Y cells were assayed by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA fragmentation, flow cytometry, Western blot, and caspase activity assays. In addition, NO, total ROS, O2â, and ONOOâ levels were measured to observe changes in NO and its possible involvement in radical induction. Cell survival was reduced to approximately 40% of control levels by SNP treatment, and this reduction was increased to 60% by low-level light irradiation. Apoptotic cells were observed in the SNP-treated group, but the frequency of these was reduced in the irradiation group. NO, O2â, total ROS, and ONOOâ levels were increased after SNP treatment, but O2â, total ROS, and ONOOâ levels were decreased after irradiation, despite the high NO concentration induced by SNP treatment. Cytochrome c was released from mitochondria of SNP-treated SH-SY5Y cells, but not of irradiated cells, resulting in a decrease in caspase-3 and -9 activity in SNP-treated cells. Finally, these results show that 635-nm irradiation, by promoting the scavenging of O2â, protected against neuronal death through blocking the mitochondrial apoptotic pathway induced by ONOOâ synthesis.
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Authors
WonBong Lim, Jae-Hyung Kim, EunByul Gook, JiSun Kim, YoungJong Ko, InAe Kim, HyukIl Kwon, HoiSoon Lim, ByungCho Jung, KyuHo Yang, NamKi Choi, MiSook Kim, SeoYune Kim, HongRan Choi, OkJoon Kim,