Klotho is an anti-aging, single-pass transmembrane protein found mainly in the kidney. Although aging is likely to be associated with DNA damage, the involvement of Klotho in protecting cells from DNA damage is still unclear. In this study, we examined DNA damage in human kidney cells and mouse kidney tissue after ionizing radiation (IR). The depletion and overexpression of Klotho in human kidney cells reduced and increased the cell survival rates after IR, respectively. The formation of γ-H2AX foci, representing DNA damage, was significantly elevated immediately after IR in cells with Klotho depletion and decreased in cells overexpressing Klotho. These results were confirmed in mouse renal tissues after IR. Quantification of DNA damage by a comet assay revealed that the Klotho knockdown significantly increased the amount of DNA damage immediately after IR, suggesting that Klotho protects chromosomal DNA from the induction of damage, rather than facilitating DNA repair. Consistent with this notion, Klotho was detected in both the nucleus and cytoplasm. In the nucleus, Klotho may serve to protect chromosomal DNA from damage, leading to its anti-aging effects.
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http://dx.doi.org/10.1093/jb/mvad001 | DOI Listing |
Environ Sci Technol
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State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
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View Article and Find Full Text PDFJ Biochem Mol Toxicol
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Department of Anatomy, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
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View Article and Find Full Text PDFACS Omega
December 2024
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal 700032, India.
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