Increased protein oxidation and decreased creatine kinase BB expression and activity after spinal cord contusion injury
Increased protein oxidation and decreased creatine kinase BB expression and activity after spinal cord contusion injury
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DOI：
10.1089/08977150252932433
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发表时间：
2002-04-01
影响因子：
4.2
通讯作者：
Geddes, JW
中科院分区：
文献类型：
--
作者：
Aksenova, M;Butterfield, DA;Geddes, JW
脊髓的创伤性损伤引发了几种继发性效应，包括氧化应激和受损的能量代谢，其在脊髓组织的生化和病理变化中起主要作用。自由基的产生和脂质过氧化已被证明是脊髓损伤后的早期事件。在本研究中，我们证明，蛋白质氧化增加大鼠脊髓组织实验性损伤后。损伤后1h，损伤中心的蛋白质羰基含量显著高于对照组（169%，p < 0.05），并在随后的4周内逐渐升高至对照组的1260%。伤后4周，脊髓尾侧和头侧的蛋白质羰基含量轻度增加（135- 138%，P < 0.05）。脊髓横截面中的蛋白质羰基的免疫细胞化学分析表明，增加的蛋白质羰基免疫反应性的震中部分相比，喙和尾部的同一动物或控制椎板切除术动物。受损脊髓组织中蛋白质羰基形成的增加与氧化敏感酶肌酸激酶BB的活性和表达的变化相关，肌酸激酶BB在维持CNS组织中ATP水平中起重要作用。中枢神经系统CK功能受损可严重加重能量代谢障碍。我们的研究结果表明，与氧化损伤相关的事件在脊髓创伤后立即触发，但在随后的4周内继续发生。这些结果表明，抗氧化治疗策略可能有利于减轻损伤的后果，并可能改善神经功能的恢复。
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 1 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.