SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway

Frontiers in Public Health

Public Health

Yunchang Cao¹  Yuqi Zhang²  Huiqian Gao²  Yashi Feng²  Fangfang Huang²  Shuting Chen³  Xiaojun Jiang³  Shaolong Feng⁴ 

[1] The Department of Molecular Biology, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, China;The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, China;The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, China;The School of Public Health, University of South China, Hengyang, China;The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, China;The School of Public Health, University of South China, Hengyang, China;The State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China;

关键词: ferroptosis;    sillica nanoparticle (SiNP);    endothelial cell (EC);    p38;    Nrf2;   

DOI  :  10.3389/fpubh.2023.1024130

 received in 2022-08-21, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionDespite of growing evidence linking silica nanoparticles (SiNPs), one of the global-top-three-produced and -used nanoparticle (NP), to human health risks, there remain many knowledge gaps over the adverse effects of SiNPs exposure on cardiovascular system and the underlying molecular mechanisms.MethodsIn this study, the ferroptotic effects of SiNPs (20 nm; 0, 25, 50, and 100 μg/mL) on human umbilical vein endothelial cells (HUVECs) and the possible molecular mechanism were studied with the corresponding biochemical and molecular biology assays.Results and discussionThe results showed that at the tested concentrations, SiNPs could decrease HUVEC viability, but the deferoxamine mesylate (an iron ion chelator) might rescue this reduction of cell viability. Also, increased levels of intracellular reactive oxygen species and enhanced mRNA expression of lipid oxidation enzymes (ACSL4 and LPCAT3) with increase in lipid peroxidation (malondialdehyde), but decreased ratios of intracellular GSH/total-GSH and mitochondrial membrane potential as well as reduced enzymatic activities of anti-oxidative enzymes (CAT, SOD, and GSH-PX), were found in the SiNPs-treated HUVECs. Meanwhile, increase in p38 protein phosphorylation and decrease in NrF2 protein phosphorylation with reduced mRNA expressions of downstream anti-oxidative enzyme genes (CAT, SOD1, GSH-PX, and GPX4) was identified in the SiNPs-exposed HUVECs. These data indicated that SiNPs exposure might induce ferroptosis in HUVECs via p38 inhibiting NrF2 pathway. Ferroptosis of HUVECs will become a useful biomarker for assessing the cardiovascular health risks of environmental contaminants.

【 授权许可】

Unknown   
Copyright © 2023 Jiang, Gao, Cao, Chen, Huang, Feng, Zhang and Feng.