Stress Response in Cerebral Ischemia and the Role of Ubiquitin

脑缺血的应激反应和泛素的作用

• 批准号: 07457305
• 负责人: KIRINO Takaaki
• 金额: $ 4.8万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457305/
• 关键词: Cerebral ischemia; Ubiquitin; Stress protein; Stress response; Cell death; Hippocampus; Mongolian gerbil; Immunostaining; 神経細胞死; 抗体; 変性蛋白

Cerebral ischemia is one of the most frequent metabolic stress to the brain. A brief period of ischemia does not kill neurons and it triggers stress response. Once stress proteins are induced, neurons acquire transient tolerance to further ischemia. Ubiquitin is one of such stress proteins. In CA1 pyramidal cells, however, free ubiquitin is depleted far before delayd neuronal death following ischemia. Our experiment has shown this by immunostaining, immunoblotting, immunoprecipitation, and immunoabsorption assays. By ELISA quantitation, we also have shown the depletion of free form of ubiq and concomitant increase in conjugated ubiquitin in CA1 neurons following ischemia. In-situ hybridization method using c-DNA complimentary to gerbil ubiquitin gene, gene expression for ubiquitin is rather enhanced following ischemia. This transient increase in transcription yet decrease in translation is also seen in hsp 70 gene following ischemia. The mechanism of delayd neuronal death of CA1 neurons is still unknown. Although the actual role of ubiquitin in neuronal death is also not known, further investigation of ubiquitin gene expression might reveal the mechanism of this form of neuronal in hippocampal Ca1 neurons.

脑缺血是大脑最常见的代谢应激之一。短暂的缺血不会杀死神经元，但会引发应激反应。一旦应激蛋白被诱导，神经元获得对进一步缺血的短暂耐受性。泛素就是其中一种应激蛋白。然而，在CA1锥体细胞中，游离泛素在缺血后延迟神经元死亡之前就已经耗尽。我们的实验通过免疫染色、免疫印迹、免疫沉淀和免疫吸收试验证明了这一点。通过ELISA定量，我们也显示了缺血后CA1神经元中泛素自由形态的消耗和伴随的共轭泛素的增加。采用与沙鼠泛素基因互补的c-DNA原位杂交方法，发现泛素基因在缺血后表达明显增强。这种短暂的转录增加而翻译减少的现象也出现在缺血后的hsp70基因中。CA1神经元延迟性死亡的机制尚不清楚。虽然泛素在神经元死亡中的实际作用尚不清楚，但对泛素基因表达的进一步研究可能揭示这种形式的神经元在海马Ca1神经元中的机制。

项目成果

Morikawa E,Zhang S-M,Seko Y.Toyoda T,Kirino T: "Treatment of focal cerebral ischemia with synthetic oligopeptide corresponding to lectin domain of selectin." Stroke. 27. 951-956 (1996)

Morikawa E，Zhang S-M，Seko Y.Toyoda T，Kirino T：“用与选择素的凝集素结构域相对应的合成寡肽治疗局灶性脑缺血。”

Morikawa E,Zhang S-M,Seko Y,Toyoda T,Kirino T: "Treatment of focal cerebral ischemia with synthetic oligopeptide corresponding to lectin domain of selectin" Stroke. 27. 951-956 (1996)

Morikawa E，Zhang S-M，Seko Y，Toyoda T，Kirino T：“用与选择素的凝集素结构域相对应的合成寡肽治疗局灶性脑缺血”中风。

Kirino T,Nakagumi T,Kanemitsu H,Tamura A: "Ischemic Tolerance." Advance in Neurology. 71. 505-511 (1996)

Kirino T、Nakagumi T、Kanemitsu H、Tamura A：“缺血耐受性。”

Ide T,Morikawa E,Kirino T: "An Immunosuppressant,FK506,protects hippocampal neurons from forebrain ischemia in the Mongolian gerbil." Neurosci Lett. 204. 157-160 (1996)

Ide T、Morikawa E、Kirino T：“一种免疫抑制剂 FK506，可以保护蒙古沙鼠的海马神经元免受前脑缺血的影响。”

Morimoto T: "Transient ischemia depletes free ubiquitin in gerbil hippocampal CA1 neurons." Am J Pathol. 148. 249-257 (1996)

Morimoto T：“短暂缺血会消耗沙鼠海马 CA1 神经元中的游离泛素。”