About: The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation     Goto   Sponge   NotDistinct   Permalink

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  • 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.
  • 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. (en)
Title
  • The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation
  • The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation (en)
skos:prefLabel
  • The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation
  • The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation (en)
skos:notation
  • RIV/00216208:11150/13:10174041!RIV14-GA0-11150___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GA304/09/1568)
http://linked.open...iv/cisloPeriodika
  • 7
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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  • 71369
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  • RIV/00216208:11150/13:10174041
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • phopsphorylation; mesenchymal stem cells; ionizing radiation; H2AX; DNA damage response; ATM kinase (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [BC26DFE20987]
http://linked.open...i/riv/nazevZdroje
  • International Journal of Radiation Biology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 89
http://linked.open...iv/tvurceVysledku
  • Havelek, Radim
  • Mokrý, Jaroslav
  • Soukup, Tomáš
  • Suchánek, Jakub
  • Vávrová, Jiřina
  • Řezáčová, Martina
  • Ćmielová, Jana
  • Köhlerová, Renata
  • Bručková, Lenka
http://linked.open...ain/vavai/riv/wos
  • 000321146200003
issn
  • 0955-3002
number of pages
http://bibframe.org/vocab/doi
  • 10.3109/09553002.2013.775530
http://localhost/t...ganizacniJednotka
  • 11150
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