Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation
Cadmium (Cd), the common environmental pollutant, primarily targets at renal proximal tubules and induces nephrotoxicity. Cellular senescence, a phenomenon of cell growth arrest and a characteristics of maladaptive cell self-repair, is associated with renal disease progression. However, whether and...
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| Format: | Article |
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Elsevier
2022-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322009381 |
| _version_ | 1818019991939710976 |
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| author | Xin Chou Xiaohu Li Zhen Min Fan Ding Kunpeng Ma Yue Shen Daoyuan Sun Qing Wu |
| author_facet | Xin Chou Xiaohu Li Zhen Min Fan Ding Kunpeng Ma Yue Shen Daoyuan Sun Qing Wu |
| author_sort | Xin Chou |
| collection | DOAJ |
| description | Cadmium (Cd), the common environmental pollutant, primarily targets at renal proximal tubules and induces nephrotoxicity. Cellular senescence, a phenomenon of cell growth arrest and a characteristics of maladaptive cell self-repair, is associated with renal disease progression. However, whether and how Cd induces renal tubular cells premature senescence is unknown. In our study, we found that Cd induced kidney damage and dysfunctions, which correlated with exacerbated tubular cell senescence, evidenced by increased senescence-associated β-galactosidase activity, the upregulated protein expression of p53 and p21Waf1/Cip1 proteins, and elevated expression and secretion of cytokines in human proximal tubular epithelial HK-2 cells in vitro and in Cd-treated mice in vivo. Moreover, a S-phase arrest and decrease in Edu positive rate were found in Cd-treated HK-2 cells. Mechanistically, Cd suppressed the expression and activity of Sirtuin-1 (SIRT1), an anti-senescence deacetylase, resulting in the accumulation of acetylated p53 and upregulation of p21Waf1/Cip1. Activation of SIRT1 significantly abolished Cd-induced premature senescence and S-phase arrest. Finally, silencing p21Waf1/Cip1 efficiently delayed premature senescence and recovered cell cycle progression. These findings indicate that Cd promotes tubular cells senescence and impairs tubular cells regeneration, resulting in kidney dysfunctions, which could be ameliorated by SIRT1 activation. |
| first_indexed | 2024-04-14T07:59:13Z |
| format | Article |
| id | doaj.art-23ed5d743c014cc390b53718ff241595 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-14T07:59:13Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-23ed5d743c014cc390b53718ff2415952022-12-22T02:04:56ZengElsevierEcotoxicology and Environmental Safety0147-65132022-10-01245114098Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylationXin Chou0Xiaohu Li1Zhen Min2Fan Ding3Kunpeng Ma4Yue Shen5Daoyuan Sun6Qing Wu7Department of Occupational Disease, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai 200433, China; School of Public Health, Fudan University, 130 Dong’An Road, Shanghai 200032, ChinaUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, ChinaDepartment of Occupational Disease, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai 200433, ChinaSchool of Public Health, Fudan University, 130 Dong’An Road, Shanghai 200032, ChinaDepartment of Occupational Disease, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai 200433, ChinaDepartment of Occupational Disease, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai 200433, ChinaDepartment of Occupational Disease, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai 200433, China; Corresponding authors.School of Public Health, Fudan University, 130 Dong’An Road, Shanghai 200032, China; Corresponding authors.Cadmium (Cd), the common environmental pollutant, primarily targets at renal proximal tubules and induces nephrotoxicity. Cellular senescence, a phenomenon of cell growth arrest and a characteristics of maladaptive cell self-repair, is associated with renal disease progression. However, whether and how Cd induces renal tubular cells premature senescence is unknown. In our study, we found that Cd induced kidney damage and dysfunctions, which correlated with exacerbated tubular cell senescence, evidenced by increased senescence-associated β-galactosidase activity, the upregulated protein expression of p53 and p21Waf1/Cip1 proteins, and elevated expression and secretion of cytokines in human proximal tubular epithelial HK-2 cells in vitro and in Cd-treated mice in vivo. Moreover, a S-phase arrest and decrease in Edu positive rate were found in Cd-treated HK-2 cells. Mechanistically, Cd suppressed the expression and activity of Sirtuin-1 (SIRT1), an anti-senescence deacetylase, resulting in the accumulation of acetylated p53 and upregulation of p21Waf1/Cip1. Activation of SIRT1 significantly abolished Cd-induced premature senescence and S-phase arrest. Finally, silencing p21Waf1/Cip1 efficiently delayed premature senescence and recovered cell cycle progression. These findings indicate that Cd promotes tubular cells senescence and impairs tubular cells regeneration, resulting in kidney dysfunctions, which could be ameliorated by SIRT1 activation.http://www.sciencedirect.com/science/article/pii/S0147651322009381CdSIRT1Proximal tubular epithelial cellCell premature senescence |
| spellingShingle | Xin Chou Xiaohu Li Zhen Min Fan Ding Kunpeng Ma Yue Shen Daoyuan Sun Qing Wu Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation Ecotoxicology and Environmental Safety Cd SIRT1 Proximal tubular epithelial cell Cell premature senescence |
| title | Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation |
| title_full | Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation |
| title_fullStr | Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation |
| title_full_unstemmed | Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation |
| title_short | Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation |
| title_sort | sirtuin 1 attenuates cadmium induced renal cell senescence through p53 deacetylation |
| topic | Cd SIRT1 Proximal tubular epithelial cell Cell premature senescence |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322009381 |
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