title: Inhibition of mitochondria-dependent apoptosis by 635-nm irradiation in sodium nitroprusside-treated SH-SY5Y cells.
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 (O(2)(-)) by a diffusion-controlled reaction to form peroxynitrite (ONOO(-)), a species that contributes to oxidative signaling and cellular apoptosis. However, the mechanism by which ONOO(-) 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 O(2)(-) scavenging with light irradiation to block ONOO(-) 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, O(2)(-), and ONOO(-) 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, O(2)(-), total ROS, and ONOO(-) levels were increased after SNP treatment, but O(2)(-), total ROS, and ONOO(-) 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 O(2)(-), protected against neuronal death through blocking the mitochondrial apoptotic pathway induced by ONOO(-) synthesis.
authors: Department of Oral Pathology, Second Stage of Brain Korea 21, School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-gu, Gwangju 500-757, Korea.
authors: WonBong
authors: W
authors: Lim
authors: Jae-Hyung
authors: JH
authors: Kim
authors: EunByul
authors: E
authors: Gook
authors: JiSun
authors: J
authors: Kim
authors: YoungJong
authors: Y
authors: Ko
authors: InAe
authors: I
authors: Kim
authors: Hyukll
authors: H
authors: Kwon
authors: HoiSoon
authors: H
authors: Lim
authors: ByungCho
authors: B
authors: Jung
authors: KyuHo
authors: K
authors: Yang
authors: NamKi
authors: N
authors: Choi
authors: MiSook
authors: M
authors: Kim
authors: SeoYune
authors: S
authors: Kim
authors: HongRan
authors: H
authors: Choi
authors: OkJoon
authors: O
authors: Kim
mesh_terms: D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000528:radiation effects; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D013481:Superoxides; D030421:Peroxynitrous Acid; D009599:Nitroprusside; D009569:Nitric Oxide; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; C022616:thiazolyl blue