lysosomal Ca2+通道的激活减轻了线粒体损伤和氧化应激
Xinghua Feng1,2, Weijie Cai1, Qian Li2
1New Cornerstone Science Laboratory and Liangzhu Laboratory, The Second Affiliated Hospital and School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
The Journal of cell biology
|November 5, 2024
概括
和脂肪酸通过增加氧化应激会损害内皮细胞. 激活TRPML1-TFEB通路可以防止这种损伤,这表明对代谢和与年龄有关的疾病的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
- 生理学 生理学 生理学
背景情况:
- 增加的自由脂肪酸和氧化应激与内皮功能障碍有关.
- 和脂肪酸与内皮损伤相关的确切机制尚不清楚.
研究的目的:
- 研究和脂肪酸,特别是棕酸 (PA) 在内皮细胞损伤中的作用.
- 探索TRPML1通道激活的潜力,作为对抗SFA诱导的氧化应激的治疗策略.
主要方法:
- 使用了用棕酸 (PA) 治疗的人体内皮细胞.
- 研究了TRPML1激动剂和基因操纵 (沉默/过度表达) 对细胞反应的影响.
- 通过TFEB激活评估线粒体的健康状况,活性氧物种 (ROS) 水平,溶酶体生物发生和线粒细胞灭菌.
主要成果:
- 棕酸诱导了线粒体分裂,并在内皮细胞中提高了细胞内ROS水平.
- TRPML1激动剂通过激活TFEB并促进溶酶体生物发生和线粒细胞衰变,减轻了PA诱导的线粒体损伤和ROS升高.
- 沉默TRPML1消除了这些保护作用,而TRPML1过度表达赋予了对PA诱导的损伤的抵抗力.
结论:
- 通过TRPML1-TFEB通路激活溶酶体是保护内皮细胞免受SFA诱导的氧化损伤的关键机制.
- 针对TRPML1-TFEB途径为与氧化应激相关的疾病,包括代谢和与年龄有关的疾病提供了潜在的治疗方法.
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