Protein nitration is associated with neuronal death following traumatic brain injury.

摘要

Recent research has focused on the role of reactive nitrogen species (RNS) in mediating neuronal degeneration following traumatic brain injury (TBI). Previously, TBI was shown to result in increased 3-nitrotyrosine (3-NT), a marker for ONOO- (Lau et al., 2006). The lateral Fluid Percussion Injury (FPI) model of moderate TBI was used to investigate the relationship between ONOO- and neuronal damage in rats. A temporal increase in protein nitration occurs in injured neurons within 1 hour following injury, peaking at 12 hours, and persisting for 24 hours. Injured neurons exhibit nitrated proteins in the cytoplasm, degenerate, and have an altered morphology compared to non-injured neurons. Protein nitration was not observed in astrocytes. Using an ex-vivo system, peroxynitrite was shown to inhibit GAPDH activity through cysteinyl oxidation. Taken together, these results suggest that peroxynitrite is formed rapidly in neurons following FPI, nitrates key neuronal proteins, and is linked with neurodegeneration.