Ischemia-reperfusion-related repair deficit after oxidative stress: implications of faulty transcripts in neuronal sensitivity after brain injury.
Ischemia-reperfusion-related repair deficit after oxidative stress: implications of faulty transcripts in neuronal sensitivity after brain injury.
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DOI：
10.1007/bf02255992
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发表时间：
2003-01
影响因子：
11
通讯作者：
Philip K. Liu
中科院分区：
文献类型：
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作者：
Philip K. Liu
心脏病是工业化国家的头号杀手。脑损伤可由于中风（脑发作）和其他心血管疾病引起的脑缺血-再灌注而发展。了解这种疾病是减少残疾和死亡的最佳途径。我们在这里提出的基因修复活动是否与缺血再灌注模型，模拟中风的雄性Long-Evans大鼠神经元死亡。已知该实验性中风模型诱导缺血性皮质坏死。脑缺血引起膜受体的过度活化和细胞外谷氨酸和细胞内钙的积累，其激活神经元一氧化氮合酶，引起脂质、蛋白质和核酸的损伤，并减少能量来源，从而导致功能退化，导致细胞死亡。恢复过程通常修复基因，很少有错误。然而，尽管有这些修复机制，缺血仍会升高氧化DNA损伤。这些事件与立即早期基因的诱导同时发生，这些基因严重激活信号传导途径中的其他晚期基因。损伤，修复和c-fosgene的转录在这里作为例子，因为Fos肽，激活蛋白1的成分之一，激活神经生长因子和修复机制。我们的研究结果表明，治疗与7-硝基吲唑，一氧化氮合酶的特异性抑制剂，已知衰减一氧化氮，氧化DNA损伤和坏死，增加完整的c-fos mRNA水平中风后。这表明，基因表达的准确性可以解释脑损伤后细胞功能的恢复。
Diseases of the heart are the No. 1 killer in industrialized countries. Brain injury can develop as a result of cerebral ischemia-reperfusion due to stroke (brain attack) and other cardiovascular diseases. Learning about the disease is the best way to reduce disability and death. We present here whether gene repair activities are associated with neuronal death in an ischemia-reperfusion model that simulates stroke in male Long-Evans rats. This experimental stroke model is known to induce necrosis in the ischemic cortex. Cerebral ischemia causes overactivation of membrane receptors and accumulation of extracellur glutamate and intracellular calcium, which activates neuronal nitric oxide synthase, causing damage to lipids, proteins, and nucleic acids, and reduces energy sources with consequent functional deterioration, leading to cell death. Restoration processes normally repair genes with few errors. However, ischemia elevates oxidative DNA lesions despite these repair mechanisms. These episodes concurrently occur with the induction of immediate-early genes that critically activate other late genes in the signal transduction pathway. Damage, repair, and transcription of the c-fosgene are presented here as examples, because Fos peptide, one of the components of activator protein 1, activates nerve growth factor and repair mechanisms. The results of our studies show that treatments with 7-nitroindazole, a specific inhibitor of nitric oxide synthase known to attenuate nitric oxide, oxidative DNA lesions, and necrosis, increase intact c-fos mRNA levels after stroke. This suggests that the accuracy of gene expression could be accounted for the recovery of cellular function after cerebral injury.