Protective Effect of Sirt1 against Radiation-Induced Damage

2021 ◽  
Author(s):  
Haoren Qin ◽  
Heng Zhang ◽  
Shiwu Zhang ◽  
Siwei Zhu ◽  
Hui Wang

Radiotherapy is an important method for the treatment of malignant tumors. It can directly or indirectly lead to the formation of free radicals and DNA damage, resulting in a series of biological effects, including tumor cell death and normal tissue damage. These radiation effects are typically accompanied by the abnormal expression of sirtuin 1 (Sirt1), which deacetylates histones and non-histones. These Sirt1 substrates, including transcription factors and some catalytic enzymes, play a crucial role in anti-oxidative stress, DNA damage repair, autophagy regulation, anti-senescence, and apoptosis, which are closely related to triggering cell defense and survival in radiation-induced damage. In this article, we review the mechanisms underlying cellular responses to ionizing radiation and the role of Sirt1 in the process, with the aim of providing a theoretical basis for protection against radiation by Sirt1 as well as novel targets for developing radioprotective agents.

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi151-vi152
Author(s):  
Quanhong Ma ◽  
Andrea Plunti ◽  
Amanda Saratsis ◽  
Rishi Lulla ◽  
Jason R Fangusaro ◽  
...  

Author(s):  
Bo Stenerlöw ◽  
Lina Ekerljung ◽  
Jörgen Carlsson ◽  
Johan Lennartsson

Author(s):  
Lieneke R. van Veelen ◽  
Tiziana Cervelli ◽  
Mandy W.M.M. van de Rakt ◽  
Arjan F. Theil ◽  
Jeroen Essers ◽  
...  

Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581877152 ◽  
Author(s):  
Miaomiao Zhang ◽  
Xiaopeng Guo ◽  
Yue Gao ◽  
Dong Lu ◽  
Wenjian Li

Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing. Senescence and apoptosis were evaluated by β-galactosidase histochemical staining and fluorescence-activated cell sorting, respectively. DNA damage was determined by long polymerase chain reaction (PCR). Telomere length and integrity were analyzed by real-time PCR and cytogenetic assay, respectively. DNA-PKcs knockdown MCF-7 cells were more sensitive to X-irradiation than control cells. Further investigation revealed that accelerated senescence is more pronounced than apoptosis in cells after radiation, particularly in DNA-PKcs knockdown cells. The cytogenetic assay and kinetics of DNA damage repair revealed that the role of telomere end-capping in DNA-PKcs, rather than DNA damage repair, was more relevant to radiosensitivity. To our knowledge, this is the first study to show that DNA-PKcs plays an important role in radiation-induced accelerated senescence via maintenance of telomere integrity in MCF-7 cells. These results could be useful for future understanding of the radiation-induced genome instability and its consequences.


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