Ambient PM2.5 exposure causes cellular senescence via DNA damage, micronuclei formation, and cGAS activation.

IF 3.6 3区医学 Q3 NANOSCIENCE & NANOTECHNOLOGY

Nanotoxicology Pub Date : 2022-08-01 DOI:10.1080/17435390.2022.2147460

Tao Wu, Shengmin Xu, Biao Chen, Lingzhi Bao, Jie Ma, Wei Han, An Xu, Kwan Ngok Yu, Lijun Wu, Shaopeng Chen

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引用次数: 4

Abstract

Ambient PM2.5 is one of the environmental risk factors and was correlated with senescence-related diseases based on the epidemiologic investigation. However, little is known about senescence induced by PM2.5 as well as the underlying mechanisms. In this study, we demonstrated that PM2.5 exposure aggravated cellular senescence in vivo and in vitro, and disrupted micronuclei (MN) played a vital role in this process. Our results suggested that the nuclear envelope (NE) of PM2.5-induced MN was ruptured. Subsequently, cGAS was found to localize to approximately 80% of the disrupted MN but few for intact MN. Upon examination of cGAMP and SA-β-Gal, the cGAS-STING pathway was found activated and related to cellular senescence induced by PM2.5. Taken together, we reported a novel finding that PM2.5 exposure causes cellular senescence via DNA damage, MN formation, and cGAS activation. These results revealed the potential toxicity of PM2.5 and its related mechanisms in cellular senescence.

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暴露在PM2.5环境中会通过DNA损伤、微核形成和cGAS激活导致细胞衰老。

环境PM2.5是环境危险因素之一，流行病学调查显示其与衰老相关疾病相关。然而，人们对PM2.5引起的衰老及其机制知之甚少。在本研究中，我们证明PM2.5暴露在体内和体外都加剧了细胞衰老，而微核破坏(MN)在这一过程中发挥了至关重要的作用。结果表明，pm2.5诱导的MN核膜(NE)破裂。随后，cGAS被发现定位于大约80%的受损MN，但很少定位于完整的MN。通过检测cGAMP和SA-β-Gal，发现cGAS-STING通路被激活，与PM2.5诱导的细胞衰老有关。综上所述，我们报告了一项新发现，即PM2.5暴露通过DNA损伤、MN形成和cGAS激活导致细胞衰老。这些结果揭示了PM2.5的潜在毒性及其在细胞衰老中的相关机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nanotoxicology 医学-毒理学

CiteScore

10.10

自引率

4.00%

发文量

审稿时长

3.5 months

期刊介绍： Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology . While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.