聚乙烯纳米塑料通过微管超稳定介导的肌功能障碍和cGAS-Sting激活促进肌肉细胞衰老
Jie Cui1, Xianlin Yue2, Yajun Zhang1
1School of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery System, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Journal of hazardous materials
|July 15, 2025
概括
聚乙烯纳米塑料 (NP) 通过破坏微管网来破坏肌肉细胞,导致器官功能障碍和细胞衰老. 重新激活Sirt2显示了缓解NP诱导肌肉损伤的潜力.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 生物化学 生物化学
背景情况:
- 聚乙烯纳米塑料 (NP) 对骨肌细胞的影响尚不清楚.
- 在NP诱导的细胞损伤背后的机制需要进一步研究.
研究的目的:
- 为了阐明NP对人类骨肌细胞的影响.
- 为了确定NP诱导的肌肉细胞损伤和衰老的分子机制.
- 探索NP毒性的潜在治疗目标.
主要方法:
- 暴露小鼠和培养的人类肌肉细胞的聚乙烯纳米塑料.
- RNA测序以分析基因表达变化.
- 微管网分析,包括管乙化和动力学.
- 评估微管组织中心 (MTOC) 功能,机械转导和器官贩运.
- 对线粒体损伤,线粒体,mtDNA泄漏和cGAS-Sting通路激活的评估.
- 调查Sirt2和HDAC6在NP诱导的微管细胞改变中的作用.
主要成果:
- 肌肉细胞吸收NP,造成显著损伤和改变细胞骨相关因素.
- 内化NP破坏了微管网,增加了管的乙化和稳定.
- 观察到MTOC功能受损,机械传导缺陷 (YAP失活) 和受损的器官贩运 (线粒体,溶解体).
- 损坏的线粒体的积累,功能障碍的线粒体,mtDNA泄漏和cGAS-Sting激活导致了细胞衰老的加速.
- NP诱导的超乙化与Sirt2和HDAC6失活有关.
- Sirt2的重新激活减少了NP诱导的损伤,衰老和细胞质NP水平.
结论:
- 聚烯纳米塑料通过破坏微管网来诱导骨肌肉细胞衰老.
- 微管动力学是NP诱导细胞损伤的关键媒介.
- 禁用Sirt2和HDAC6驱动NP诱导的微管过度稳定和随后的毒性.
- Sirt2的重新激活是针对纳米塑料诱导的肌肉损伤的潜在治疗策略.
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