Protein and DNA oxidation in spinal injury: Neurofilaments - An oxidation target

This study measured the time courses of protein and DNA oxidation following spinal cord injury (SCI) in rats and characterized oxidative degradation o f proteins. Protein carbonyl content-a marker of protein oxidation-signific antly increased at 3-9 h postinjury and the ratio 8-hydroxy-2-deoxyguanosin e/deoxyguanosine-an indicator of DNA oxidation-was significantly higher at 3-6 h postinjury in the injured cords than in the sham controls. This sugge sts that oxidative modification of proteins and DNA contributes to secondar y damage in SCI. Densities of selected bands on coomassie-stained gels indi cated that most proteins were degraded. Neurofilament protein (NFP) was par ticularly evaluated immunohistochemically; its light chain (NFP-68) was gra dually degraded in nerve fibers, neuron bodies, and large dendrites followi ng SCI. A mixture of Mn (III) tetrakis (4-benzoic acid) porphyrin (10 mg/kg )-a novel SOD mimetic-and nitro-L-arginine (1 mg/kg)-an inhibitor of nitric oxide synthase-injected intraperitoneally, increased NFP-68 immunoreactivi ty and the numbers of NFP-positive nerve fibers post-SCI, correlating NFP d egradation in SCI to free radical-triggered oxidative damage for the first time. Therefore, blockage of protein and DNA oxidation in the secondary inj ury stage may improve long-term recovery-important information for developm ent of the SCI therapies. (C) 2001 Elsevier Science Inc.