Antioxidants prevent particulate matter-induced senescence of lung fibroblasts

Particulate matter (PM) contributes to human diseases, particularly lung disease; however, the molecular mechanism of its action is yet to be determined. Herein, we found that prolonged PM exposure induced the cellular senescence of normal lung fibroblasts via a DNA damage-mediated response. This PM...

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Main Authors: Sein Jin, Sung-Jin Yoon, Na-Young Jung, Wang Sik Lee, Jinyoung Jeong, Young-Jun Park, Wantae Kim, Doo-Byoung Oh, Jinho Seo
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023013865
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author Sein Jin
Sung-Jin Yoon
Na-Young Jung
Wang Sik Lee
Jinyoung Jeong
Young-Jun Park
Wantae Kim
Doo-Byoung Oh
Jinho Seo
author_facet Sein Jin
Sung-Jin Yoon
Na-Young Jung
Wang Sik Lee
Jinyoung Jeong
Young-Jun Park
Wantae Kim
Doo-Byoung Oh
Jinho Seo
author_sort Sein Jin
collection DOAJ
description Particulate matter (PM) contributes to human diseases, particularly lung disease; however, the molecular mechanism of its action is yet to be determined. Herein, we found that prolonged PM exposure induced the cellular senescence of normal lung fibroblasts via a DNA damage-mediated response. This PM-induced senescence (PM-IS) was only observed in lung fibroblasts but not in A549 lung adenocarcinoma cells. Mechanistic analysis revealed that reactive oxygen species (ROS) activate the DNA damage response signaling axis, increasing p53 phosphorylation, ultimately leading to cellular senescence via an increase in p21 expression without affecting the p16-pRB pathway. A549 cells, instead, were resistant to PM-IS due to the PM-induced ROS production suppression. Water-soluble antioxidants, such as vitamin C and N-Acetyl Cysteine, were found to alleviate PM-IS by suppressing ROS production, implying that antioxidants are a promising therapeutic intervention for PM-mediated lung pathogenesis.
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spelling doaj.art-9bc55958b13348ceaf42d4ae66e76f022023-04-05T08:21:10ZengElsevierHeliyon2405-84402023-03-0193e14179Antioxidants prevent particulate matter-induced senescence of lung fibroblastsSein Jin0Sung-Jin Yoon1Na-Young Jung2Wang Sik Lee3Jinyoung Jeong4Young-Jun Park5Wantae Kim6Doo-Byoung Oh7Jinho Seo8Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea; Department of Biochemistry, Chungnam National University, Daejeon, 34134, South KoreaEnvironmental Disease Research Center, KRIBB, Daejeon, 34141, South KoreaAging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea; Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South KoreaEnvironmental Disease Research Center, KRIBB, Daejeon, 34141, South KoreaEnvironmental Disease Research Center, KRIBB, Daejeon, 34141, South Korea; Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South KoreaEnvironmental Disease Research Center, KRIBB, Daejeon, 34141, South Korea; Department of Biomolecular Science, KRIBB School of Bioscience, UST, Daejeon, 34113, South KoreaDepartment of Biochemistry, Chungnam National University, Daejeon, 34134, South KoreaAging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea; Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South Korea; Corresponding author. Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South Korea.Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea; Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South Korea; Corresponding author. Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea.Particulate matter (PM) contributes to human diseases, particularly lung disease; however, the molecular mechanism of its action is yet to be determined. Herein, we found that prolonged PM exposure induced the cellular senescence of normal lung fibroblasts via a DNA damage-mediated response. This PM-induced senescence (PM-IS) was only observed in lung fibroblasts but not in A549 lung adenocarcinoma cells. Mechanistic analysis revealed that reactive oxygen species (ROS) activate the DNA damage response signaling axis, increasing p53 phosphorylation, ultimately leading to cellular senescence via an increase in p21 expression without affecting the p16-pRB pathway. A549 cells, instead, were resistant to PM-IS due to the PM-induced ROS production suppression. Water-soluble antioxidants, such as vitamin C and N-Acetyl Cysteine, were found to alleviate PM-IS by suppressing ROS production, implying that antioxidants are a promising therapeutic intervention for PM-mediated lung pathogenesis.http://www.sciencedirect.com/science/article/pii/S2405844023013865Particulate matterCellular senescenceReactive oxygen speciesDNA damage ResponseAntioxidants
spellingShingle Sein Jin
Sung-Jin Yoon
Na-Young Jung
Wang Sik Lee
Jinyoung Jeong
Young-Jun Park
Wantae Kim
Doo-Byoung Oh
Jinho Seo
Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
Heliyon
Particulate matter
Cellular senescence
Reactive oxygen species
DNA damage Response
Antioxidants
title Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
title_full Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
title_fullStr Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
title_full_unstemmed Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
title_short Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
title_sort antioxidants prevent particulate matter induced senescence of lung fibroblasts
topic Particulate matter
Cellular senescence
Reactive oxygen species
DNA damage Response
Antioxidants
url http://www.sciencedirect.com/science/article/pii/S2405844023013865
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