Airborne nitro-PAHs induce Nrf2/ARE defense system against oxidative stress and promote inflammatory process by activating PI3K/Akt pathway in A549 cells
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| Titel: | Airborne nitro-PAHs induce Nrf2/ARE defense system against oxidative stress and promote inflammatory process by activating PI3K/Akt pathway in A549 cells |
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| Autoren: | Shang, Yu, Zhou, Qian, Wang, Tiantian, Jiang, Yuting, Zhong, Yufang, Qian, Guangren, Zhu, Tong, Qiu, Xinghua, An, Jing |
| Weitere Verfasser: | An, J (reprint author), Shanghai Univ, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China., Shanghai Univ, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China., Peking Univ, Coll Environm Sci & Engn, State Key Lab Environm Simulat & Pollut Control, Beijing 100871, Peoples R China. |
| Quelle: | SCI |
| Verlagsinformationen: | TOXICOLOGY IN VITRO |
| Publikationsjahr: | 2017 |
| Bestand: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| Schlagwörter: | Nitro-PAHs, Oxidative stress, Cytokines, Nrf2/ARE, PI3K/Akt, POLYCYCLIC AROMATIC-HYDROCARBONS, AMBIENT PARTICULATE MATTER, AIR-POLLUTION, DNA-DAMAGE, SIGNALING PATHWAY, DIESEL EXHAUST, NITRATED-PAHS, IN-VITRO, EXPOSURE, HEALTH |
| Beschreibung: | Ambient particulate matter (PM) is a worldwide health issue of concern. However, limited information is available regarding the toxic contributions of the nitro-derivatives of polycyclic aromatic hydrocarbons (nitro-PAHs). This study intend to examine whether 1-nitropyrene (1-NP) and 3-nitrofluoranthene (3-NF) could activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) antioxidant defense system, and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway participates in regulating pro-inflammatory responses in A549 cells. Firstly, 1-NP and 3-NF concentration-dependently induced cellular apoptosis, reactive oxygen species (ROS) generation, DNA damage, S phase cell cycle arrest and differential expression of related cytokine genes. Secondly, 1-NP and 3-NF activated the Nrf2/ARE defense system, as evidenced by increased protein expression levels and nuclear translocation of transcription factor Nrf2, elevated Nrf2/ARE binding activity, up-regulated expression of the target gene heme oxygenase-1 (HO-1). Significantly increased protein expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and phosphorylation level of Akt indicated that the PI3K/Akt pathway was activated during pro-inflammatory process. Further, both PI3K inhibitor (LY294002) and Akt inhibitor (MK-2206) reversed the elevated TNF-alpha expression to control level. Our results suggested that Nrf2/ARE pathway activation might cause an initiation step in cellular protection against oxidative stress caused by nitro-PAHs, and the PI3K/Akt pathway participated in regulating inflammatory responses. ; Joint NSFC-ISF Research Program - National Natural Science Foundation of China [41561144007]; Joint NSFC-ISF Research Program - Israel Science Foundation [41561144007]; National Natural Science Foundation of China [21107068, 91543123]; Innovative Research Team in University [IRT13078]; special fund of State Key Joint Laboratory of Environment Simulation and Pollution Control ... |
| Publikationsart: | journal/newspaper |
| Sprache: | English |
| Relation: | 1904706; http://hdl.handle.net/20.500.11897/470685; WOS:000409395000009 |
| DOI: | 10.1016/j.tiv.2017.06.017 |
| Verfügbarkeit: | https://hdl.handle.net/20.500.11897/470685 https://doi.org/10.1016/j.tiv.2017.06.017 |
| Dokumentencode: | edsbas.E26F9ECE |
| Datenbank: | BASE |
Nájsť tento článok vo Web of Science | Abstract: | Ambient particulate matter (PM) is a worldwide health issue of concern. However, limited information is available regarding the toxic contributions of the nitro-derivatives of polycyclic aromatic hydrocarbons (nitro-PAHs). This study intend to examine whether 1-nitropyrene (1-NP) and 3-nitrofluoranthene (3-NF) could activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) antioxidant defense system, and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway participates in regulating pro-inflammatory responses in A549 cells. Firstly, 1-NP and 3-NF concentration-dependently induced cellular apoptosis, reactive oxygen species (ROS) generation, DNA damage, S phase cell cycle arrest and differential expression of related cytokine genes. Secondly, 1-NP and 3-NF activated the Nrf2/ARE defense system, as evidenced by increased protein expression levels and nuclear translocation of transcription factor Nrf2, elevated Nrf2/ARE binding activity, up-regulated expression of the target gene heme oxygenase-1 (HO-1). Significantly increased protein expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and phosphorylation level of Akt indicated that the PI3K/Akt pathway was activated during pro-inflammatory process. Further, both PI3K inhibitor (LY294002) and Akt inhibitor (MK-2206) reversed the elevated TNF-alpha expression to control level. Our results suggested that Nrf2/ARE pathway activation might cause an initiation step in cellular protection against oxidative stress caused by nitro-PAHs, and the PI3K/Akt pathway participated in regulating inflammatory responses. ; Joint NSFC-ISF Research Program - National Natural Science Foundation of China [41561144007]; Joint NSFC-ISF Research Program - Israel Science Foundation [41561144007]; National Natural Science Foundation of China [21107068, 91543123]; Innovative Research Team in University [IRT13078]; special fund of State Key Joint Laboratory of Environment Simulation and Pollution Control ... |
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| DOI: | 10.1016/j.tiv.2017.06.017 |