Antioxidants prevent particulate matter-induced senescence of lung fibroblasts

Sein Jin; Sung-Jin Yoon; Na-Young Jung; Wang Sik Lee; Jinyoung Jeong; Young-Jun Park; Wantae Kim; Doo-Byoung Oh; Jinho Seo

doi:10.1016/j.heliyon.2023.e14179

Antioxidants prevent particulate matter-induced senescence of lung fibroblasts

Heliyon. 2023 Mar 1;9(3):e14179. doi: 10.1016/j.heliyon.2023.e14179. eCollection 2023 Mar.

Authors

Sein Jin^{1

2}, Sung-Jin Yoon³, Na-Young Jung^{1

4}, Wang Sik Lee³, Jinyoung Jeong^{3

4}, Young-Jun Park^{3

5}, Wantae Kim², Doo-Byoung Oh^{1

4}, Jinho Seo^{1

4}

Affiliations

¹ Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea.
² Department of Biochemistry, Chungnam National University, Daejeon, 34134, South Korea.
³ Environmental Disease Research Center, KRIBB, Daejeon, 34141, South Korea.
⁴ Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, South Korea.
⁵ Department of Biomolecular Science, KRIBB School of Bioscience, UST, Daejeon, 34113, South Korea.

Abstract

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.

Keywords: Antioxidants; Cellular senescence; DNA damage Response; Particulate matter; Reactive oxygen species.