Increased Protein Oxidation and Decreased Creatine Kinase BB Expression and Activity after Spinal Cord Contusion Injury

Abstract

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.

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

“…The major function of KCRB is to maintain a normal supply of ATP to the CNS tissues. Thus, a reduction in KCRB is indicative of an impairment of energy metabolism in the SCI tissue, and this result is consistent with a previous study (60). Most importantly, aFGF was able to attenuate this effect and potentially improve and restore neuronal function.…”

Antioxidant Therapies for Acute Spinal Cord Injury

“…Using immunoblotting techniques that identify DNPH-modified protein carbonyl moieties, an increase in protein oxidation has been documented by at least three laboratories [23,27,28]. However, it must be noted that the DNPH-based carbonyl assay does not distinguish between protein carbonyl groups produced by direct iron-driven amino acid oxidation and protein binding of LP-generated aldehydic breakdown products, which can also leave exposed carbonyl groups that can react with DNPH [2].…”

Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone

“…13 Their reactivity is the result of an unpaired electron in their outer atomic orbital. 8 It is the product of this reactivity that contributes to neuronal injury by reacting with endogenous proteins, 1 lipids, and nucleic acids, 3 causing structural changes through reconfiguration and degradation. Oxidative stress initiates lipid peroxidation cascades that lead to the damage of highly vulnerable cell membranes during the first few days after injury.…”