Increased protein oxidation and decreased creatine kinase BB expression and activity after spinal cord contusion injury.
Traumatic injury to the spinal cord triggers several secondary effects, including oxidative stress and compromised energy metabolism, which play a major role in biochemical and pathological changes in spinal cord tissue. Free radical generation and lipid peroxidation have been shown to be early events subsequent to spinal cord injury. In the present study, we demonstrated that protein oxidation increases in rat spinal cord tissue after experimental injury. As early as h after injury, the level of protein carbonyls at the injury epicenter was significantly higher than in control (169%, p < 0.05) and increased gradually over the next 4 weeks to 1260% of control level. Both caudal and rostral parts of the injured spinal cord demonstrated a mild increase of protein carbonyls by 4 weeks postinjury (135-138%, p < 0.05). Immunocytochemical analysis of protein carbonyls in the spinal cord cross-sections showed increased protein carbonyl immunoreactivity in the epicenter section compared to rostral and caudal sections of the same animal or control laminectomy animals. Increased protein carbonyl formation in damaged spinal cord tissue was associated with changes in activity and expression of an oxidative sensitive enzyme, creatine kinase BB, which plays an important role in the maintenance of ATP level in the CNS tissue. Damage to CK function in the CNS may severely aggravate the impairment of energy metabolism. The results of our study indicate that events associated with oxidative damage are triggered immediately after spinal cord trauma but continue to occur over the subsequent 4 weeks. These results suggest that antioxidant therapeutic strategies may be beneficial to lessen the consequences of the injury and potentially improve the restoration of neurological function.
Aksenova
Marina
M
Department of Pharmacology, University of Kentucky, Lexington 40506-0055, USA.
Butterfield
D Allan
DA
Zhang
Shu-Xin
SX
Underwood
Mark
M
Geddes
James W
JW
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013904:Thoracic Vertebrae / Q000378:metabolism
D009419:Nerve Tissue Proteins; D003402:Creatine Kinase