Publikace detail

The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation

Rok: 2013

Druh publikace: článek v odborném periodiku

Název zdroje: International Journal of Radiation Biology

Název nakladatele: Informa Healthcare UK

Místo vydání: London

Strana od-do: 501-511

Tituly:

Jazyk	Název	Abstrakt	Klíčová slova
cze	The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation	Purpose : This study evaluates early changes in human mesenchymal stem cells (MSC) isolated from dental pulp and periodontal ligament after gamma-irradiation and the effect of ataxia-telangiectasia mutated (ATM) inhibition. Methods : MSC were irradiated with 2 and 20 Gy by Co-60. For ATM inhibition, specific inhibitor KU55933 was used. DNA damage was measured by Comet assay and gamma H2AX detection. Cell cycle distribution and proteins responding to DNA damage were analyzed 2-72 h after the irradiation. Results : The irradiation of MSC causes an increase in gamma H2AX; the phosphorylation was ATM-dependent. Irradiation activates ATM kinase, and the level of p53 protein is increased due to its phosphorylation on serine15. While this phosphorylation of p53 is ATM-dependent in MSC, the increase in p53 was not prevented by ATM inhibition. A similar trend was observed for Chk1 and Chk2. The increase in p21 is greater without ATM inhibition. ATM inhibition also does not fully abrogate the accumulation of irradiated MSC in the G2-phase of the cell-cycle. Conclusions : In irradiated MSC, double-strand breaks are tagged quickly by gamma H2AX in an ATM-dependent manner. Although phosphorylations of p53(ser15), Chk1(ser345) and Chk2(thr68) are ATM-dependent, the overall amount of these proteins increases when ATM is inhibited. In both types of MSC, ATM-independent mechanisms for cell-cycle arrest in the G2-phase are triggered.	ATM kinase; DNA damage response; H2AX; ionizing radiation; mesenchymal stem cells; phopsphorylation
eng	The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation	Purpose : This study evaluates early changes in human mesenchymal stem cells (MSC) isolated from dental pulp and periodontal ligament after gamma-irradiation and the effect of ataxia-telangiectasia mutated (ATM) inhibition. Methods : MSC were irradiated with 2 and 20 Gy by Co-60. For ATM inhibition, specific inhibitor KU55933 was used. DNA damage was measured by Comet assay and gamma H2AX detection. Cell cycle distribution and proteins responding to DNA damage were analyzed 2-72 h after the irradiation. Results : The irradiation of MSC causes an increase in gamma H2AX; the phosphorylation was ATM-dependent. Irradiation activates ATM kinase, and the level of p53 protein is increased due to its phosphorylation on serine15. While this phosphorylation of p53 is ATM-dependent in MSC, the increase in p53 was not prevented by ATM inhibition. A similar trend was observed for Chk1 and Chk2. The increase in p21 is greater without ATM inhibition. ATM inhibition also does not fully abrogate the accumulation of irradiated MSC in the G2-phase of the cell-cycle. Conclusions : In irradiated MSC, double-strand breaks are tagged quickly by gamma H2AX in an ATM-dependent manner. Although phosphorylations of p53(ser15), Chk1(ser345) and Chk2(thr68) are ATM-dependent, the overall amount of these proteins increases when ATM is inhibited. In both types of MSC, ATM-independent mechanisms for cell-cycle arrest in the G2-phase are triggered.	ATM kinase; DNA damage response; H2AX; ionizing radiation; mesenchymal stem cells; phopsphorylation

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