Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway

被引：13

作者：

Qing, Tao-lin ^{[1
]}

Yan, Lang ^{[1
]}

Wang, Shao-kang ^{[2
]}

Dai, Xiao-yu ^{[1
]}

Ren, Li-jun ^{[1
]}

Zhang, Ji-qian-zhu ^{[1
]}

Shi, Wen-jing ^{[1
]}

Zhang, Xiao-fang ^{[1
]}

Wang, Mei-tang ^{[2
]}

Chen, Ji-kuai ^{[1
]}

Zhu, Jiang-bo ^{[1
,3
]}

机构：

[1] Second Mil Med Univ, Fac Naval Med, Dept Hlth Toxicol, Shanghai 200433, Peoples R China

[2] Second Mil Med Univ, Changhai Hosp, Dept Emergency, Shanghai, Peoples R China

[3] Second Mil Med Univ, Dept Hlth Toxicol, 800 Xiangyin Rd, Shanghai 200433, Peoples R China

来源：

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY | 2023年 / 252卷

基金：

中国国家自然科学基金;

关键词：

Multi-walled carbon nanotubes; Reactive oxygen species; Nrf2; Keap1; Celastrol; NRF2; EXPRESSION; KEAP1; INFLAMMATION; ACTIVATION;

D O I：

10.1016/j.ecoenv.2023.114623

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

引用

页数：10

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