Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments

被引:76
作者
Cmielova, Jana [1 ]
Havelek, Radim [1 ]
Soukup, Tomas [2 ]
Jiroutova, Alena [1 ]
Visek, Benjamin [2 ]
Suchanek, Jakub [3 ]
Vavrova, Jirina [5 ]
Mokry, Jaroslav [2 ]
Muthna, Darina [1 ]
Bruckova, Lenka [2 ]
Filip, Stanislav [4 ]
English, Denis [6 ]
Rezacova, Martina [1 ]
机构
[1] Charles Univ Prague, Dept Med Biochem, Fac Med Hradec Kralove, Hradec Kralove 50038, Czech Republic
[2] Charles Univ Prague, Dept Histol & Embryol, Fac Med Hradec Kralove, Hradec Kralove 50038, Czech Republic
[3] Charles Univ Prague, Dept Dent, Fac Med Hradec Kralove, Hradec Kralove 50038, Czech Republic
[4] Charles Univ Prague, Dept Radiotherapy & Oncol, Fac Med Hradec Kralove, Hradec Kralove 50038, Czech Republic
[5] Univ Def, Fac Mil Hlth Sci, Dept Radiobiol, Hradec Kralove, Czech Republic
[6] Univ S Florida, Dept Neurosurg, Florida Fdn Dev Res, Palmetto, FL USA
关键词
Irradiation; premature senescence; mesenchymal stem cell; bone marrow; periodontal ligament; HUMAN DENTAL-PULP; IONIZING-RADIATION; DNA-DAMAGE; CELLULAR SENESCENCE; GROWTH ARREST; CYCLE ARREST; IN-VIVO; P53; PHOSPHORYLATION; IRRADIATION;
D O I
10.3109/09553002.2012.666001
中图分类号
Q [生物科学];
学科分类号
090105 [作物生产系统与生态工程];
摘要
Purpose: Mesenchymal stem cells isolated from bone marrow (BM-MSC) and periodontal ligament (PLSC) are cells with high proliferative potential and ability to self-renewal. Characterization of these cells under genotoxic stress conditions contributes to the assessment of their prospective usage. The aim of our study was to evaluate changes in BM-MSC and PLSC caused by ionizing radiation. Methods: Human BM-MSC and PLSC were irradiated with the doses up to 20 Gy by Co-60 and observed 13 days; viability, proliferation, apoptosis and senescence induction, and changes in expression and phosphorylation status of related proteins were studied. Results : Irradiation with the doses up to 20 Gy significantly reduces proliferation, but has no significant effect on cell viability. The activation of tumor suppressor protein 53 (p53) and its phosphorylations on serines 15 and 392 were detected from the first day after irradiation by 20 Gy and remained elevated to day 13. Expression of cyclin-dependent kinases inhibitor 1A (p21(Cip1/Waf1)) increased. The cell cycle was arrested in G2 phase. Instead of apoptosis we have detected hallmarks of stress-induced premature senescence: increase in cyclin-dependent kinases inhibitor 2A (p16(INK4a)) and increased activity of senescence-associated beta-galactosidase. Conclusion : Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.
引用
收藏
页码:393 / 404
页数:12
相关论文
共 43 条
[1]
Aldridge DR, 1998, CANCER RES, V58, P2817
[2]
THE EFFECT OF RADIATION ON TEETH - A CLINICAL, HISTOLOGIC AND MICRORADIOGRAPHIC STUDY [J].
ANNEROTH, G ;
HOLM, LE ;
KARLSSON, G .
INTERNATIONAL JOURNAL OF ORAL SURGERY, 1985, 14 (03) :269-274
[3]
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].
Bakkenist, CJ ;
Kastan, MB .
NATURE, 2003, 421 (6922) :499-506
[4]
The signals and pathways activating cellular senescence [J].
Ben-Porath, I ;
Weinberg, RA .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2005, 37 (05) :961-976
[5]
Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after γ-irradiation [J].
Brugarolas, J ;
Moberg, K ;
Boyd, SD ;
Taya, Y ;
Jacks, T ;
Lees, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :1002-1007
[6]
Cellular senescence: when bad things happen to good cells [J].
Campisi, Judith ;
di Fagagna, Fabrizio d'Adda .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (09) :729-740
[7]
Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J].
Canman, CE ;
Lim, DS ;
Cimprich, KA ;
Taya, Y ;
Tamai, K ;
Sakaguchi, K ;
Appella, E ;
Kastan, MB ;
Siliciano, JD .
SCIENCE, 1998, 281 (5383) :1677-1679
[8]
The sensitivity of human mesenchymal stem cells to ionizing radiation [J].
Chen, Miao-Fen ;
Lin, Ching-Tai ;
Chen, Wen-g Chen ;
Yang, Cheng-Ta ;
Chen, Chih-g Chen ;
Liao, Shuen-Kuei ;
Liu, Jacqueline Ming ;
Lu, Chang-Hsien ;
Lee, Kuan-Der .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 66 (01) :244-253
[9]
Protocols to detect senescence-associated beta-galactosidase (SA-βgal) activity, a biomarker of senescent cells in culture and in vivo [J].
Debacq-Chainiaux, Florence ;
Erusalimsky, Jorge D. ;
Campisi, Judith ;
Toussaint, Olivier .
NATURE PROTOCOLS, 2009, 4 (12) :1798-1806
[10]
Nuclear accumulation of p21Cip1 the onset of mitosis:: a role at the G2/M-phase transition [J].
Dulic, V ;
Stein, GH ;
Far, DF ;
Reed, SI .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (01) :546-557