Tempol protection of spinal cord mitochondria from peroxynitrite-induced oxidative damage.
Peroxynitrite (PN)-mediated mitochondrial dysfunction has been implicated in the secondary injury process after traumatic spinal cord injury (SCI). This study investigated the detrimental effects of the PN donor SIN-1 (3-morpholinosydnonimine) on isolated healthy spinal cord mitochondria and the protective effects of tempol, a catalytic scavenger of PN-derived radicals. A 5 min exposure of the mitochondria to SIN-1 caused a dose-dependent decrease in the respiratory control ratio (RCR) that was accompanied by significant increases in complex I-driven states II and IV respiration rates and decreases in states III and V. These impairments occurred together with an increase in mitochondrial protein 3-nitrotyrosine (3-NT), but not in lipid peroxidation (LP)-related 4-hydroxynonenal (4-HNE). Tempol significantly antagonized the respiratory effects of SIN-1 in parallel with an attenuation of 3-NT levels. These results show that the exogenous PN donor, SIN-1, rapidly causes mitochondrial oxidative damage and complex I dysfunction identical to traumatic spinal cord mitochondrial impairment and that this is mainly due to tyrosine nitration. Consistent with that, the protection of mitochondrial respiratory function by tempol is associated with a decrease in 3-NT levels in mitochondrial proteins also similar to the previously reported antioxidant actions of tempol in traumatically-injured spinal cord mitochondria.
Xiong
Yiqin
Y
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA.
Singh
Indrapal N
IN
Hall
Edward D
ED
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D030421:Peroxynitrous Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000187:drug effects
C443112:3-nitrosotyrosine; D000975:Antioxidants; D003497:Cyclic N-Oxides; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D013113:Spin Labels; D030421:Peroxynitrous Acid; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; C001803:tempol