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Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
Previous studies have shown that long-term exposure to fine particulate matter (PM(2.5)) increases the morbidity and mortality of pulmonary diseases such as asthma, chronic obstructive pulmonary disease and pulmonary emphysema. Oxidative stress and inflammation play key roles in pulmonary damage cau...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104929/ https://www.ncbi.nlm.nih.gov/pubmed/33967806 http://dx.doi.org/10.3389/fphar.2021.662664 |
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author | Ding, Hao Jiang, Menghui Li, Daochuan Zhao, Yanjie Yu, Dianke Zhang, Rong Chen, Wen Pi, Jingbo Chen, Rui Cui, Lianhua Zheng, Yuxin Piao, Jinmei |
author_facet | Ding, Hao Jiang, Menghui Li, Daochuan Zhao, Yanjie Yu, Dianke Zhang, Rong Chen, Wen Pi, Jingbo Chen, Rui Cui, Lianhua Zheng, Yuxin Piao, Jinmei |
author_sort | Ding, Hao |
collection | PubMed |
description | Previous studies have shown that long-term exposure to fine particulate matter (PM(2.5)) increases the morbidity and mortality of pulmonary diseases such as asthma, chronic obstructive pulmonary disease and pulmonary emphysema. Oxidative stress and inflammation play key roles in pulmonary damage caused by PM(2.5). Nuclear factor erythroid 2-related factor 2 (Nrf2) could regulate the expression of antioxidant and anti-inflammatory genes and is pivotal for protection against PM(2.5)-induced oxidative stress. In this study, a real-ambient exposure system was constructed with the outdoor ambient air in north China. Wild-type (WT) and Nrf2(−/−) (KO) mice were exposed to the real-ambient system for six weeks. After PM(2.5) exposure, our data showed that the levels of inflammatory factors and malondialdehyde were significantly increased in WT and KO mice. Moreover, the lung function and pathological phenotype of the WT mice were altered but there was no obvious change in the Nrf2(−/−) mice. To further explore the potential molecular mechanisms, we performed RNA-sequencing. The RNA-sequence analysis results showed that the CYP450 pathway in the first ten pathways of KEGG was related to the metabolism of PM(2.5). In WT and KO mice, the expression of CYP2E1 in the CYP450 pathway showed opposite trends after PM(2.5) exposure. The data showed that the expression of the CYP2E1 gene in WT-PM mice increased while it decreased in KO-PM; the expression of the CYP2E1 protein showed a similar trend. CYP2E1 is primarily distributed in the endoplasmic reticulum (ER) where it could metabolize various exogenous substances attached to PM(2.5) and produce highly toxic oxidation products closely related to ER stress. Consistently, the expression level of GRP94, a biomarker of ER stress, was increased in WT mice and reduced in KO mice under PM(2.5) exposure. Persistent ER stress is a mechanism that causes lung damage under PM(2.5) exposure. Nrf2 facilitates lung injury during PM(2.5) exposure and CYP2E1 metabolism is involved in this process. |
format | Online Article Text |
id | pubmed-8104929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81049292021-05-08 Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−) Ding, Hao Jiang, Menghui Li, Daochuan Zhao, Yanjie Yu, Dianke Zhang, Rong Chen, Wen Pi, Jingbo Chen, Rui Cui, Lianhua Zheng, Yuxin Piao, Jinmei Front Pharmacol Pharmacology Previous studies have shown that long-term exposure to fine particulate matter (PM(2.5)) increases the morbidity and mortality of pulmonary diseases such as asthma, chronic obstructive pulmonary disease and pulmonary emphysema. Oxidative stress and inflammation play key roles in pulmonary damage caused by PM(2.5). Nuclear factor erythroid 2-related factor 2 (Nrf2) could regulate the expression of antioxidant and anti-inflammatory genes and is pivotal for protection against PM(2.5)-induced oxidative stress. In this study, a real-ambient exposure system was constructed with the outdoor ambient air in north China. Wild-type (WT) and Nrf2(−/−) (KO) mice were exposed to the real-ambient system for six weeks. After PM(2.5) exposure, our data showed that the levels of inflammatory factors and malondialdehyde were significantly increased in WT and KO mice. Moreover, the lung function and pathological phenotype of the WT mice were altered but there was no obvious change in the Nrf2(−/−) mice. To further explore the potential molecular mechanisms, we performed RNA-sequencing. The RNA-sequence analysis results showed that the CYP450 pathway in the first ten pathways of KEGG was related to the metabolism of PM(2.5). In WT and KO mice, the expression of CYP2E1 in the CYP450 pathway showed opposite trends after PM(2.5) exposure. The data showed that the expression of the CYP2E1 gene in WT-PM mice increased while it decreased in KO-PM; the expression of the CYP2E1 protein showed a similar trend. CYP2E1 is primarily distributed in the endoplasmic reticulum (ER) where it could metabolize various exogenous substances attached to PM(2.5) and produce highly toxic oxidation products closely related to ER stress. Consistently, the expression level of GRP94, a biomarker of ER stress, was increased in WT mice and reduced in KO mice under PM(2.5) exposure. Persistent ER stress is a mechanism that causes lung damage under PM(2.5) exposure. Nrf2 facilitates lung injury during PM(2.5) exposure and CYP2E1 metabolism is involved in this process. Frontiers Media S.A. 2021-04-23 /pmc/articles/PMC8104929/ /pubmed/33967806 http://dx.doi.org/10.3389/fphar.2021.662664 Text en Copyright © 2021 Ding, Jiang, Li, Zhao, Yu, Zhang, Chen, Pi, Chen, Cui, Zheng and Piao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Ding, Hao Jiang, Menghui Li, Daochuan Zhao, Yanjie Yu, Dianke Zhang, Rong Chen, Wen Pi, Jingbo Chen, Rui Cui, Lianhua Zheng, Yuxin Piao, Jinmei Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−) |
title | Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
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title_full | Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
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title_fullStr | Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
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title_full_unstemmed | Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
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title_short | Effects of Real-Ambient PM(2.5) Exposure on Lung Damage Modulated by Nrf2(−/−)
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title_sort | effects of real-ambient pm(2.5) exposure on lung damage modulated by nrf2(−/−) |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104929/ https://www.ncbi.nlm.nih.gov/pubmed/33967806 http://dx.doi.org/10.3389/fphar.2021.662664 |
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