Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells.
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| Natura: | Artículo científico |
| Lingua: | en |
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Free radical research
2024
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| _version_ | 1868266270350114817 |
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| author | Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun |
| author_facet | Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun |
| collection | PubMed - marine biology |
| contents | Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells. Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun Humans NF-E2-Related Factor 2 Cellular Senescence Particulate Matter Retinal Pigment Epithelium Proto-Oncogene Proteins c-akt Mitochondria Reactive Oxygen Species Down-Regulation Oxidative Stress Epithelial Cells Cell Line Urban aerosol particulate matter (UPM) is widespread in the environment, and its concentration continues to increase. Several recent studies have reported that UPM results in premature cellular senescence, but few studies have investigated the molecular basis of UPM-induced senescence in retinal pigment epithelial (RPE) cells. In this study, we primarily evaluated UPM-induced premature senescence and the protective function of nuclear factor erythroid 2-related factor 2 (Nrf2) in human RPE ARPE-19 cells. The findings indicated that UPM exposure substantially induced premature cellular senescence in ARPE-19 cells, as observed by increased β-galactosidase activity, expression levels of senescence-associated marker proteins, and senescence-associated phenotypes. Such UPM-induced senescence is associated with mitochondrial oxidative stress-mediated phosphatidylinositol 3'-kinase/Akt/Nrf2 downregulation. Sulforaphane-mediated Nrf2 activation Sulforaphane-mediated upregulation of phosphorylated Nrf2 suppressed the decrease in its target antioxidant gene, NAD(P)H quinone oxidoreductase 1, under UPM, which notably prevented ARPE-19 cells from UPM-induced cellular senescence. By contrast, Nrf2 knockdown exacerbated cellular senescence and promoted oxidative stress. Collectively, our results demonstrate the regulatory role of Nrf2 in UPM-induced senescence of RPE cells and suggest that Nrf2 is a potential molecular target. |
| format | Artículo científico |
| id | pubmed_39645666 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Free radical research |
| record_format | pubmed |
| spellingShingle | Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells. Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun Humans NF-E2-Related Factor 2 Cellular Senescence Particulate Matter Retinal Pigment Epithelium Proto-Oncogene Proteins c-akt Mitochondria Reactive Oxygen Species Down-Regulation Oxidative Stress Epithelial Cells Cell Line Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells. Park, Beom Su Bang, EunJin Hwangbo, Hyun Kim, Gi-Young Cheong, JaeHun Choi, Yung Hyun Humans NF-E2-Related Factor 2 Cellular Senescence Particulate Matter Retinal Pigment Epithelium Proto-Oncogene Proteins c-akt Mitochondria Reactive Oxygen Species Down-Regulation Oxidative Stress Epithelial Cells Cell Line Urban aerosol particulate matter (UPM) is widespread in the environment, and its concentration continues to increase. Several recent studies have reported that UPM results in premature cellular senescence, but few studies have investigated the molecular basis of UPM-induced senescence in retinal pigment epithelial (RPE) cells. In this study, we primarily evaluated UPM-induced premature senescence and the protective function of nuclear factor erythroid 2-related factor 2 (Nrf2) in human RPE ARPE-19 cells. The findings indicated that UPM exposure substantially induced premature cellular senescence in ARPE-19 cells, as observed by increased β-galactosidase activity, expression levels of senescence-associated marker proteins, and senescence-associated phenotypes. Such UPM-induced senescence is associated with mitochondrial oxidative stress-mediated phosphatidylinositol 3'-kinase/Akt/Nrf2 downregulation. Sulforaphane-mediated Nrf2 activation Sulforaphane-mediated upregulation of phosphorylated Nrf2 suppressed the decrease in its target antioxidant gene, NAD(P)H quinone oxidoreductase 1, under UPM, which notably prevented ARPE-19 cells from UPM-induced cellular senescence. By contrast, Nrf2 knockdown exacerbated cellular senescence and promoted oxidative stress. Collectively, our results demonstrate the regulatory role of Nrf2 in UPM-induced senescence of RPE cells and suggest that Nrf2 is a potential molecular target. |
| title | Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells. |
| topic | Humans NF-E2-Related Factor 2 Cellular Senescence Particulate Matter Retinal Pigment Epithelium Proto-Oncogene Proteins c-akt Mitochondria Reactive Oxygen Species Down-Regulation Oxidative Stress Epithelial Cells Cell Line |
| url | https://pubmed.ncbi.nlm.nih.gov/39645666/ |