通过调节USP3-SIRT3-P53轴,PM2.5有助于肺上皮质衰老和铁亡
Ning Li1, Rui Xiong1, Guorui Li1
1Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Free radical biology & medicine
|June 22, 2023
概括
颗粒物2.5 (PM2.5) 肺损伤涉及上皮细胞衰老和铁亡. 赛尔图因3 (SIRT3) 通过脱乙P53来保护,提供了一个潜在的治疗标.
科学领域:
- 环境健康 环境健康
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 颗粒物2.5 (PM2.5) 暴露与肺炎和纤维化有关.
- PM2.5诱导肺上皮细胞衰老和铁亡,这是肺损伤中的关键过程.
- 赛尔图因3 (SIRT3) 是线粒体脱甲基酶,具有抗氧化和抗衰老的作用.
研究的目的:
- 研究SIRT3在PM2.5引起的肺损伤中的作用.
- 阐明涉及SIRT3,P53和铁亡的潜在机制.
- 评估针对USP3-SIRT3-P53轴的治疗潜力.
主要方法:
- 在II型膜上皮细胞 (AT2) 中SIRT3基因衰减和过度表达.
- 在小鼠和体外AT2细胞培养中的PM2.5暴露模型.
- RNA测序,基因和基因组的京都百科全书 (KEGG) 分析,以及西方 blot.
- 使用黑素对SIRT3的药理激活.
主要成果:
- 暴露在PM2.5下调了SIRT3蛋白水平和肺组织和AT2细胞中的活性.
- SIRT3缺乏症加剧了PM2.5引起的炎症,纤维化,衰老和铁亡.
- 过度表达SIRT3改善了这些效应,而其缺乏可以调节铁亡和衰老标志物.
- 通过DNA损伤,PM2.5增加了P53的乙化;SIRT3在K320处去乙化P53,降低了其活性.
- 通过降低USP3的调节,PM2.5降低了SIRT3,影响了蛋白酶体通路.
- 作为一种SIRT3激动剂的黑可以缓解PM2.5诱导的衰老和铁亡.
结论:
- 通过减轻衰老和铁亡,SIRT3对PM2.5诱导的肺损伤起着保护作用.
- USP3-SIRT3-P53轴是PM2.5引起的肺损伤的一个关键途径.
- 针对USP3-SIRT3-P53轴是PM2.5相关的肺部疾病的潜在治疗策略.
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