对于保护性ER应激反应而言,一种依赖于血栓素的途径
Jeffrey M Lynch1, Marjorie Maillet, Davy Vanhoutte
1Department of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati, OH 45247, USA.
Cell
|June 12, 2012
概括
血栓蛋白质 (Thbs) 蛋白质通过增强内分泌网膜 (ER) 应激反应来保护心脏损伤. Thbs4 特别促进了适应性ER压力,增强了ER功能,并在疾病期间保护心脏.
科学领域:
- 心血管生物学 心血管生物学
- 细胞应激反应的应激反应
- 分子医学是分子医学.
背景情况:
- 血栓蛋白质 (Thbs) 是在组织损伤和重塑的部位上调节的蛋白质.
- 在疾病期间,内质网膜 (ER) 的应激反应被激活,调节蛋白质平衡.
- 在疾病适应过程中,Thbs和ER压力之间的潜在联系尚未被探索.
研究的目的:
- 为了研究血栓蛋白 (Thbs) 作为适应性ER应激反应的效应者的作用.
- 确定Thbs4在心脏损伤和适应不良中所起的作用.
- 阐明Thbs影响ER功能和细胞保护的机制.
主要方法:
- 使用心脏特异的Thbs4转基因和Thbs4淘汰赛小鼠模型.
- 分析了适应性ER应激反应因子和ER形态.
- 在体内和体外研究了Thbs与激活转录因子6α (Atf6α) 之间的相互作用.
- 评估心脏损伤和适应不良的表型.
主要成果:
- Thbs4转基因小鼠显示出对心肌损伤的保护,而Thbs4(-/-) 小鼠则被敏感化.
- Thbs诱导导致了适应性ER压力因子概况和ER扩张.
- Thbs与Atf6α的ER光内域结合,促进其核转位.
- Thbs4(-/-) 小鼠表现出淡的Atf6α激活,而Thbs4介导的保护依赖于Atf6α.
结论:
- 血栓松素 (Thbs) 在细胞内作为适应性ER应激反应的ER居住因子而起作用.
- Thbs4通过调节Atf6α来增强ER功能,在心脏重塑中起着保护作用.
- 这种机制强调了Thbs作为涉及ER压力的心血管疾病的潜在治疗点.
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