Klotho protects chromosomal DNA from radiation-induced damage.

J Biochem

Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8551, Japan.

Published: April 2023

AI Article Synopsis

  • * Research showed that reducing Klotho levels in human kidney cells increased DNA damage and decreased cell survival after exposure to ionizing radiation (IR), while overexpressing Klotho had the opposite effect.
  • * The study suggests that Klotho protects chromosomal DNA from damage rather than repairing it, as evidenced by its presence in both the nucleus and cytoplasm, potentially contributing to its anti-aging properties.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129345PMC
http://dx.doi.org/10.1093/jb/mvad001DOI Listing

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