拉帕素复合体2的机械标保护心脏免受缺血性损伤
Mirko Völkers1, Mathias H Konstandin, Shirin Doroudgar
1From SDSU Heart Institute, Department of Biology, San Diego State University, San Diego, CA.
Circulation
|September 7, 2013
概括
拉巴胺素 (mTOR) 信号传递的机械标在缺血性心脏病中至关重要. 将平衡转向mTOR复合体2 (mTORC2),同时抑制mTOR复合体1 (mTORC1),可以保护心脏免受损伤.
科学领域:
- 心血管生物学 心血管生物学
- 分子信号传输的方法
- 细胞病理生理学
背景情况:
- 拉巴胺素 (mTOR) 途径的机械性标涉及两个复合体,mTORC1和mTORC2.2.
- 在缺血性心脏病中,mTOR信号放松有助于心肌损伤.
- 对于mTORC1和mTORC2在缺血性心脏病的发病过程中的不同作用尚不清楚.
研究的目的:
- 研究mTORC1和mTORC2在缺血性心脏病的背景下的不同作用.
- 为了确定调节mTORC1和mTORC2信号之间的平衡是否会影响心脏损伤.
主要方法:
- 在培养心肌细胞和小鼠模型中利用了联合药理和分子方法.
- 使用特定抑制剂 (Torin1,Rictor抑制,PRAS40抑制) 操纵的mTORC1和mTORC2信号平衡.
- 评估心肌细胞亡和肌肉损伤后心肌梗塞诱导的缺血条件.
主要成果:
- 药理上抑制mTORC1和mTORC2 (Torin1) 都会加剧心肌细胞亡和组织损伤.
- 主要的mTORC1信号传递 (Rictor抑制) 也增加了心脏损伤.
- 通过抑制mTORC1 (PRAS40) 优选增强mTORC2信号传递,降低心肌细胞亡和组织损伤.
结论:
- 选择性增强mTORC2信号传递,加上mTORC1抑制,表明在缺血性心脏病中具有保护作用.
- 这种调制代表了治疗心肌损伤的潜在新疗法策略.
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