心肌细胞成熟改变了分子应激反应能力,并决定了线粒体功能障碍时的细胞存活率
Nina Schraps1, Michaela Tirre2, Simon Pyschny2
1Department of Pediatric Cardiology, Justus Liebig University, Gießen, Germany.
Free radical biology & medicine
|January 24, 2024
概括
不成熟的心肌细胞比成年人更好地容忍线粒体功能障碍,激活保护它们的压力反应. 这种弹性可以解释为什么胎儿心能承受压力,并有助于新生儿心的再生能力.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体生物学 线粒体生物学
- 细胞应激反应的应激反应
背景情况:
- 心肌细胞成熟涉及将能量代谢从葡萄糖转变为脂肪酸,并增加线粒体质量.
- 心肌细胞在分化过程中处理活性氧物种 (ROS) 的能力尚不清楚.
- 线粒体功能障碍和ROS与各种心脏疾病有关.
研究的目的:
- 为了研究心肌细胞成熟如何影响细胞生存和应激反应对线粒体功能障碍.
- 为了比较胚胎,新生儿和成人心肌细胞对ROS诱导剂的耐受性.
- 阐明不同发育阶段心肌细胞应激反应背后的分子机制.
主要方法:
- 主要小鼠心肌细胞 (胚胎,新生儿,成年人) 在体外培养.
- 线粒体功能被抑制使用rotenone (复合物I),抗菌素A (复合物III) 和寡菌素 (复合物V).
- 评估了细胞存活率,线粒体形态和分子应激反应 (抗氧化,综合应激反应,ER应激).
主要成果:
- 胚胎和新生儿心肌细胞耐受复杂III和V抑制,但易受复杂I抑制.
- 成年心肌细胞在复杂III抑制后显示出快速解体.
- 胚胎心肌细胞激活了抗氧化和综合应激反应,而成年心肌细胞没有.
结论:
- 与成人心肌细胞相比,不成熟心肌细胞对线粒体功能障碍的耐力较高.
- 不成熟心肌细胞中增强的应激反应可能会保护发育中的心脏免受子宫内应激.
- 这种弹性可能有助于胚胎和新生儿心脏中观察到的再生潜力.
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