二氧化颗粒诱导DNA氧化损伤,激活小脑中AIM2-介导的PANoptosis在小鼠中
Hao Cai1, Meichen Gao1, Tong Xu1
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
Chemico-biological interactions
|October 3, 2024
概括
二氧化 (SiO2) 纳米颗粒通过诱导氧化应激和DNA损伤引起神经毒性,引发PANoptosis. 较小的SiO2颗粒具有更大的毒性,突出了与这些新材料相关的风险.
科学领域:
- 神经毒理学 神经毒理学
- 材料科学 材料科学 材料科学
- 细胞生物学 细胞生物学
背景情况:
- 二氧化 (SiO2) 颗粒越来越多地用于各种应用.
- SiO2颗粒的潜在神经毒性作用需要进行彻底的调查.
- 了解SiO2粒子毒性的机制对于人类安全至关重要.
研究的目的:
- 研究不同尺寸SiO2颗粒在小脑组织和细胞上的毒理机制.
- 阐明氧化应激,DNA损伤和PANoptosis在SiO2诱导的神经毒性的作用.
- 为了确定SiO2粒子大小与神经毒性程度之间的相关性.
主要方法:
- 在体内口服给小鼠21天的SiO2颗粒 (1μm,300nm,50nm).
- 在实验室培养小脑星细胞 (C8-D1A细胞).
- 检测氧化应激,DNA损伤 (彗星测定) 和PANoptosis通路 (免疫光,西部斑点,qRT-PCR).
主要成果:
- SiO2颗粒诱导了氧化应激和随后的DNA氧化损伤.
- 异常DNA激活了AIM2 (在黑色素瘤2中不存在),导致PANoptosome复合体组装和PANoptosis.
- 神经毒性和损伤与SiO2颗粒大小相反相关,较小的颗粒更有毒.
结论:
- SiO2颗粒通过一种涉及氧化应激,DNA损伤和PANoptosis的机制引起小脑损伤.
- 这项研究扩大了对神经毒理学中PANoptosis的理解.
- 这些发现支持制定安全标准,以减轻暴露于SiO2颗粒的风险.
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