减少氧化蛋白折叠减轻了衰老,通过将ER-to-nucleus H2 O2释放到最低,从而减轻了衰老
Fang Cheng1,2, Qianzhao Ji2,3, Lu Wang1
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
EMBO reports
|June 12, 2023
概括
由蛋白质二硫化异合酶 (PDI) 驱动的氧化蛋白折叠,有助于细胞衰老. 降低PDI水平可以缓解人间介质干细胞和其他衰老模型中的衰老.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 生物化学 生物化学
背景情况:
- 氧化蛋白在内质网膜 (ER) 中折叠产生过氧化 (H2O2).
- 氧化蛋白折叠和细胞衰老之间的联系尚未得到充分理解.
研究的目的:
- 研究氧化蛋白折叠在细胞衰老中的作用.
- 为了确定蛋白质二硫化异构酶 (PDI) 是否参与人类介质干细胞 (hMSCs) 的衰老.
主要方法:
- 在老年hMSC中分析PDI积累.
- 在hMSCs和其他衰老细胞模型中遗传删除PDI.
- 测量ER衍生的H2O2泄漏到核中的测量.
- 评估SERPINE1表达作为衰老标志物的评估.
主要成果:
- 在老化的hMSC中积累了PDI,其删除减少了hMSC的衰老.
- PDI淘汰会降低氧化蛋白折叠率和ER衍生的H2O2核泄漏.
- 在多个衰老细胞模型中,PDI耗尽降低了SERPINE1表达,这是一个关键的衰老驱动器.
结论:
- 由PDI调解的氧化蛋白折叠促进细胞衰老.
- 针对PDI和氧化蛋白折叠可能为衰老和相关疾病提供治疗策略.
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