通过调节自细胞,TRPM2可以预防西斯普拉丁诱导的急性损伤和线粒体功能障碍
Binfeng Yu1,2, Lini Jin1,3, Xi Yao1
1Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine; Institute of Nephrology, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China.
Theranostics
|August 31, 2023
概括
暂时受体潜力梅拉斯2 (TRPM2) 能够预防西斯普拉丁诱导的急性损伤 (AKI). 由于TRPM2缺乏,它会通过Ca2+-AKT-mTOR通路阻断自,从而使损伤恶化.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 西斯是一种重要的化疗药物,但由于毒性,其使用受到限制.
- 暂时受体潜在的 Melastatin 2 (TRPM2) 通道与氧化应激和自有关.
- 在西斯普拉丁诱导的损伤中TRPM2的作用尚不清楚.
研究的目的:
- 调查TRPM2在西斯普拉丁诱导的急性损伤 (AKI) 中的作用.
- 阐明涉及TRPM2,氧化应激和自的潜在分子机制.
主要方法:
- 使用了野生类型和Trpm2-淘汰赛小鼠和初级细胞.
- 评估了西斯普拉丁诱导的损伤,细胞损伤和线粒体损伤.
- 采用RNA测序,免疫光,免疫阻塞和流细胞计.
主要成果:
- TRPM2淘汰赛加剧了西斯胺诱导的功能障碍,管状损伤和亡.
- 线粒体损伤和亡在TRPM2-缺乏模型中恶化,但通过抗氧化剂和mTOR抑制剂得到改善.
- 由于TRPM2缺乏,它通过阻断Ca2+流入和激活AKT-mTOR信号,导致自身食受损.
结论:
- TRPM2在西斯普拉丁诱导的AKI中起着保护作用.
- 保护机制包括调节Ca2+-AKT-mTOR信号和自.
- 这些发现为损伤病原和潜在的治疗标提供了新的见解.
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