CALPAIN AND CASPASE PROTEOLYSIS OF BRAIN SPECTRIN

脑血影蛋白的钙蛋白酶和半胱天冬酶蛋白水解

• 批准号: 2523240
• 负责人: BRIAN R. PIKE
• 金额: $ 2.54万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2523240
• 关键词: brain injury; calpain; cellular pathology; endopeptidases; laboratory rat; pathologic process; proteolysis; spectrin; western blottings

Traumatic brain injury (TBI) is a significant health care issue in the United States affecting more than 2 million persons annually, with approximately 500,000 hospital admissions. Rapid and sustained calpain activation is thought to be an important intracellular event mediating the neuropathological response to TBI. In addition, the interleukin- 1beta-converting enzyme (ICE) family of cysteine proteases (recently renamed caspases) has also been posited as having an important role in the pathophysiology of TBI. However, regional and temporal profiles of these proteases in TBI have not been fully characterized. The Specific Aims of this proposal are to examine calpain-and caspase-mediated proteolysis of the neuronal cytoskeletal protein, alpha-spectrin, in various brain regions from 15 minutes to 90 days following rodent TBI, and to correlate the profile of spectrin degradation to neuromorphological alterations. A novel feature of this project is the employment of an antibody that concurrently immunolabels native alpha- spectrin (240 kD), the calpain-specific spectrin breakdown product (SBDP) (145 kD), and the caspase-specific SBDP (120 kD) on Western blots. The Specific Aims are focused towards addressing the central hypothesis that TBI causes rapid and enduring regionally- and temporally-specific patterns of calpain- and caspase-mediated alpha- spectrin proteolysis in brain regions known to be vulnerable to neuronal insult. This investigation will contribute to the growing body of knowledge regarding the pathophysiological mechanisms contributing to cellular, parenchymal, and behavioral morbidity following TBI.

创伤性脑损伤（TBI）是一个重要的医疗保健问题， 美国每年影响200多万人， 约50万人入院。 快速和持续的钙蛋白酶 激活被认为是介导细胞内的重要事件， 创伤性脑损伤的神经病理学反应此外，白细胞介素- 1 β-转化酶（ICE）家族的半胱氨酸蛋白酶（最近 重命名为半胱天冬酶）也被认为在 TBI的病理生理学。 然而， TBI中的这些蛋白酶还没有被完全表征。 具体 本提案的目的是检查钙蛋白酶和半胱天冬酶介导的 神经元细胞骨架蛋白α-血影蛋白的蛋白水解， 啮齿动物TBI后15分钟至90天的各种脑区域， 并将血影蛋白降解谱与 神经形态学改变 该项目的一个新特点是 使用同时免疫标记天然α- 血影蛋白（240 kD），钙蛋白酶特异性血影蛋白分解产物 （SBDP）（145 kD）和半胱天冬酶特异性SBDP（120 kD）。 污点。 具体目标的重点是解决中央 假设TBI导致快速和持久的区域性-和 钙蛋白酶和半胱天冬酶介导的α- 已知易受神经元损伤的脑区域中血影蛋白的蛋白水解 侮辱。 这项调查将有助于不断增长的机构， 关于病理生理机制的知识有助于 TBI后的细胞、实质和行为发病率。