过度炼引起多 (ADP-ribose) 聚合酶-1激活和全球蛋白质PARylation驱动肌肉功能障碍和性能受损
Barbara M Crisol1, Matheus B Rocha1, Beatriz Franco2
1Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, Brazil.
过度炼可能导致过度训练综合征. 研究人员发现,骨肌中PARP1 (Poly(ADP-ribose) 聚合酶1的过度激活有助于这种综合征,这表明PARP1是潜在的治疗点.
科学领域:
- 运动生理学 运动生理学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 过度训练综合征 (OTS) 是由于过度炼和不充分的恢复引起的,导致疲劳和性能下降.
- 肌肉细胞内导致OTS的特定分子机制尚未完全理解.
研究的目的:
- 为了研究在过度训练综合征中的性能损害背后的分子机制.
- 识别潜在的分子点,以预防或治疗OTS.
主要方法:
- 对同源BXD小鼠菌株和被过度训练的小鼠模型进行了多omics分析.
- 过度炼方案也适用于人类受试者.
- 在骨肌肉中评估了PARP1 (Poly(ADP-ribose) 聚合酶1) 活性和蛋白质水平.
- 用药学抑制和基因废除PARP1来评估其在OTS中的作用.
主要成果:
- 骨肌中Parp1的基因表达升高与BXD小鼠菌株中OTS特征相关.
- 过度训练的小鼠和人类在骨肌肉中增加了PARP1蛋白和异常蛋白PARylation.
- OTS导致线粒体功能降低,肌肉过敏症,肌肉纤维大小减少和肌肉病相关的基因表达.
- 在小鼠中抑制或消去PARP1,保护小鼠免受性能损害和OTS症状的影响.
结论:
- 过度激活PARP1与短期和长期过度运动引起的肌肉异常有关.
- PARP1代表了预防和治疗过度训练综合征的潜在治疗标.
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