STRESS PROTEIN INDUCTION IN BRAIN AFTER ISCHEMIA

缺血后大脑中应激蛋白的诱导

• 批准号: 3846233
• 负责人: T S NOWAK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3846233
• 关键词: cerebral cortex; cerebral ischemia /hypoxia; gene expression; genetic transcription; genetic translation; hippocampus; immunocytochemistry; in situ hybridization; laboratory rat; messenger RNA; microtubule associated protein; neurons; protein biosynthesis; stress proteins; transcription factor

Ongoing studies continue to focus on the role of altered gene expression in postischemic pathophysiology. Specifically, transcriptional and translational expression of the stress protein, hsp7O, and transcription factors, Fos and Jun, are evaluated by comparison of in situ hybridization and immunocytochemistry. Perhaps the most significant result has been the observation that threshold ischemic , resulting in an induced tolerance to subsequent challenges, are correlated with hsp7O and Jun expression in the vulnerable CA l neurons that are protected. Protein synthesis deficits that follow severe initial insults apparently result in the failure to translate mRNAs even though they may be induced. Since Jun in turn functions to regulate the transcriptional expression of other genes, this finding begins to indicate the complexity of genetic reprogramming that must be associated with induced tolerance phenomena. Other changes in gene expression have been evaluated after ischemia, notably that of microtubule-associated protein 2 (MAP -2). An mRNA encoding a truncated protein, MAP-2c, is induced in cortex and hippocampal CA1 regions that show delayed damage in a rat cardiac arrest model. In contrast to stress protein and proto-oncogene expression that largely occur in surviving neurons, MAP-2c appears to constitute a selective marker for severely injured neurons after ischemia.

正在进行的研究继续关注基因表达改变的作用 在缺血后病理生理学中的应用 具体而言，转录和 应激蛋白hsp 7 O的翻译表达和转录 因子Fos和Jun，通过比较原位 杂交和免疫细胞化学。 也许最重要的 结果是观察到阈值缺血，导致 诱导的对后续挑战的耐受性，与hsp 7 O相关， Jun在受保护的脆弱CA 1神经元中的表达。 严重的初始损伤后的蛋白质合成缺陷 导致不能翻译mRNA，即使它们可以被诱导。 由于Jun反过来又调节转录表达， 其他基因，这一发现开始表明遗传的复杂性， 重编程必须与诱导耐受现象相关。 在局部缺血后已经评估了基因表达的其他变化， 特别是微管相关蛋白2（MAP-2）。 的mRNA 编码截短的蛋白质MAP-2c，在皮质中被诱导， 大鼠心脏骤停后海马CA 1区延迟损伤 模型 与应激蛋白和原癌基因表达相反， MAP-2c主要发生在存活的神经元中，MAP-2c似乎构成了 缺血后严重损伤神经元的选择性标记物。