端粒酶逆转录酶通过HL-1细胞中的p53/PGC-1α通路调节细胞内Ca2+和线粒体功能
Chuanbin Liu1, Kun Lin2, Zhonghui Xie3
1Western Medical Branch of PLA General Hospital, 100853 Beijing, China.
Frontiers in bioscience (Landmark edition)
|July 31, 2024
概括
端粒酶逆转录酶 (TERT) 在维持心肌细胞功能和预防心房动 (AF) 中起着至关重要的作用. TERT调节 (Ca2+) 稳态和线粒体功能,这表明对AF的潜在治疗益处.
科学领域:
- 心血管生物学 心血管生物学
- 细胞电生理学 细胞电生理学
- 线粒体功能的功能
背景情况:
- 端粒缩短与心血管衰老和心房动 (AF) 的风险增加有关.
- 端粒酶逆转录酶 (TERT) 维持端粒长度,并在临床前模型中显示出心脏保护作用.
- TERT在心肌细胞电生理学和处理中的确切作用尚不清楚.
研究的目的:
- 调查TERT在调节Ca2+稳态和心房肌细胞中线粒体功能的作用.
- 阐明潜在的分子机制,包括p53/PGC-1α通路.
主要方法:
- HL-1心房肌细胞被设计为TERT过度表达或使用lentiviruses沉默.
- 电生理学性质 (动作潜力的持续时间,L型Ca2+电流) 使用补丁进行了评估.
- 细胞内Ca2+度,线粒体膜潜力 (MMP) 和氧气消耗率 (OCR) 通过流细胞计和海马试验进行测量.
主要成果:
- TERT沉默导致了Ca2+过载,缩短了动力潜力的持续时间,减少了L型Ca2+电流,减少了MMP和OCR,增加了活性氧物种 (ROS).
- TERT静音还降低了SERCA2a,CaV1.2和NCX1.1.1.的表达.
- TERT调节了p53和氧酶增殖剂激活受体马协活性剂1-α (PGC-1α) 表达,PGC-1α作为一个关键的介质.
结论:
- TERT缺乏导致Ca2+过载和线粒体功能障碍,可能导致与年龄相关的AF.
- 过度表达TERT通过改善Ca2+处理和线粒体功能,显示出抗心律失常的潜力.
- p53/PGC-1α通路是TERT调节心肌细胞电生理学和功能的关键机制,为AF提供了一个新的治疗点.
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