Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway
As the most common heavy metal pollutant, hexavalent chromium [Cr(VI)] has caused serious environmental pollution and health damage. Although the toxic effect of Cr(VI) has been widely studied, and oxidative stress has been confirmed to be the main mechanism of its cytotoxicity, the toxicity of Cr(V...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321007260 |
| _version_ | 1819113919514411008 |
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| author | Yu Ma Siwen Li Shuzi Ye Sixuan Tang Die Hu Lai Wei Fang Xiao |
| author_facet | Yu Ma Siwen Li Shuzi Ye Sixuan Tang Die Hu Lai Wei Fang Xiao |
| author_sort | Yu Ma |
| collection | DOAJ |
| description | As the most common heavy metal pollutant, hexavalent chromium [Cr(VI)] has caused serious environmental pollution and health damage. Although the toxic effect of Cr(VI) has been widely studied, and oxidative stress has been confirmed to be the main mechanism of its cytotoxicity, the toxicity of Cr(VI) to human immune system remains to be elucidated. Neutrophil extracellular traps (NETs) participate in the innate immune response, and the release of NETs is considered to be the most important part of the extracellular killing mechanism. We demonstrated in this study that Cr(VI) inhibited the formation of NETs in rat peripheral blood and induced neutrophils apoptosis by inhibiting the AMP-activated protein kinase (AMPK) signaling pathway. Cr(VI)-induced inhibition of NETs was accompanied by down-regulated myeloperoxidase (MPO)/Histones-3 (H3) protein expressions and decreased NETs-associated intracellular and extracellular DNA levels in the neutrophils. Metformin (Met), as an AMPK activator, triggered autophagy and thus alleviated the inhibitory effect of Cr(VI) on NETs. At the same time, Met can reduce the intracellular reactive oxygen species (ROS) level by activating the AMPK/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway, thus alleviating Cr(VI)-induced neutrophils apoptosis. In conclusion, this study elucidated the mechanism of Cr(VI)-induced neutrophils toxicity and the role of AMPK as a key regulatory signal, which could provide valuable experimental basis for the prevention and treatment of related diseases in Cr(VI)-exposed populations. |
| first_indexed | 2024-12-22T04:37:03Z |
| format | Article |
| id | doaj.art-7f2d4682847146cca867831d3a5e68ee |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-22T04:37:03Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-7f2d4682847146cca867831d3a5e68ee2022-12-21T18:38:52ZengElsevierEcotoxicology and Environmental Safety0147-65132021-10-01223112614Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathwayYu Ma0Siwen Li1Shuzi Ye2Sixuan Tang3Die Hu4Lai Wei5Fang Xiao6Xiangya School of Public Health, Central South University, Changsha 410078, PR ChinaXiangya School of Public Health, Central South University, Changsha 410078, PR ChinaXiangya School of Public Health, Central South University, Changsha 410078, PR ChinaXiangya School of Public Health, Central South University, Changsha 410078, PR ChinaXiangya School of Public Health, Central South University, Changsha 410078, PR ChinaXiangya School of Public Health, Central South University, Changsha 410078, PR ChinaCorresponding author.; Xiangya School of Public Health, Central South University, Changsha 410078, PR ChinaAs the most common heavy metal pollutant, hexavalent chromium [Cr(VI)] has caused serious environmental pollution and health damage. Although the toxic effect of Cr(VI) has been widely studied, and oxidative stress has been confirmed to be the main mechanism of its cytotoxicity, the toxicity of Cr(VI) to human immune system remains to be elucidated. Neutrophil extracellular traps (NETs) participate in the innate immune response, and the release of NETs is considered to be the most important part of the extracellular killing mechanism. We demonstrated in this study that Cr(VI) inhibited the formation of NETs in rat peripheral blood and induced neutrophils apoptosis by inhibiting the AMP-activated protein kinase (AMPK) signaling pathway. Cr(VI)-induced inhibition of NETs was accompanied by down-regulated myeloperoxidase (MPO)/Histones-3 (H3) protein expressions and decreased NETs-associated intracellular and extracellular DNA levels in the neutrophils. Metformin (Met), as an AMPK activator, triggered autophagy and thus alleviated the inhibitory effect of Cr(VI) on NETs. At the same time, Met can reduce the intracellular reactive oxygen species (ROS) level by activating the AMPK/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway, thus alleviating Cr(VI)-induced neutrophils apoptosis. In conclusion, this study elucidated the mechanism of Cr(VI)-induced neutrophils toxicity and the role of AMPK as a key regulatory signal, which could provide valuable experimental basis for the prevention and treatment of related diseases in Cr(VI)-exposed populations.http://www.sciencedirect.com/science/article/pii/S0147651321007260Hexavalent chromium [Cr(VI)]Neutrophil extracellular traps (NETs)ApoptosisAMP-activated protein kinase (AMPK) signaling pathwayReactive oxygen species (ROS) |
| spellingShingle | Yu Ma Siwen Li Shuzi Ye Sixuan Tang Die Hu Lai Wei Fang Xiao Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway Ecotoxicology and Environmental Safety Hexavalent chromium [Cr(VI)] Neutrophil extracellular traps (NETs) Apoptosis AMP-activated protein kinase (AMPK) signaling pathway Reactive oxygen species (ROS) |
| title | Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway |
| title_full | Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway |
| title_fullStr | Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway |
| title_full_unstemmed | Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway |
| title_short | Hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via AMPK signaling pathway |
| title_sort | hexavalent chromium inhibits the formation of neutrophil extracellular traps and promotes the apoptosis of neutrophils via ampk signaling pathway |
| topic | Hexavalent chromium [Cr(VI)] Neutrophil extracellular traps (NETs) Apoptosis AMP-activated protein kinase (AMPK) signaling pathway Reactive oxygen species (ROS) |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321007260 |
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