SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway
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 mec...
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Frontiers Media S.A.
2023-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1024130/full |
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| author | Xiaojun Jiang Xiaojun Jiang Huiqian Gao Yunchang Cao Shuting Chen Shuting Chen Fangfang Huang Yashi Feng Yuqi Zhang Shaolong Feng Shaolong Feng Shaolong Feng |
| author_facet | Xiaojun Jiang Xiaojun Jiang Huiqian Gao Yunchang Cao Shuting Chen Shuting Chen Fangfang Huang Yashi Feng Yuqi Zhang Shaolong Feng Shaolong Feng Shaolong Feng |
| author_sort | Xiaojun Jiang |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-04-10T16:41:11Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Public Health |
| spelling | doaj.art-8ed00e4bc4044632a160bd535f9b5b032023-02-08T07:12:42ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-02-011110.3389/fpubh.2023.10241301024130SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathwayXiaojun Jiang0Xiaojun Jiang1Huiqian Gao2Yunchang Cao3Shuting Chen4Shuting Chen5Fangfang Huang6Yashi Feng7Yuqi Zhang8Shaolong Feng9Shaolong Feng10Shaolong Feng11The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe School of Public Health, University of South China, Hengyang, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe Department of Molecular Biology, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe School of Public Health, University of South China, Hengyang, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin, ChinaThe School of Public Health, University of South China, Hengyang, ChinaThe State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, ChinaIntroductionDespite 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.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1024130/fullferroptosissillica nanoparticle (SiNP)endothelial cell (EC)p38Nrf2 |
| spellingShingle | Xiaojun Jiang Xiaojun Jiang Huiqian Gao Yunchang Cao Shuting Chen Shuting Chen Fangfang Huang Yashi Feng Yuqi Zhang Shaolong Feng Shaolong Feng Shaolong Feng SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway Frontiers in Public Health ferroptosis sillica nanoparticle (SiNP) endothelial cell (EC) p38 Nrf2 |
| title | SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway |
| title_full | SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway |
| title_fullStr | SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway |
| title_full_unstemmed | SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway |
| title_short | SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway |
| title_sort | sinps induce ferroptosis in huvecs through p38 inhibiting nrf2 pathway |
| topic | ferroptosis sillica nanoparticle (SiNP) endothelial cell (EC) p38 Nrf2 |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1024130/full |
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