ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence

详细信息    查看全文

• 作者：Jun Park ; Yong Hwa Jo ; Chang Hoon Cho ; Wonchae Choe ; Insug Kang ; Hyung Hwan Baik ; Kyung-Sik Yoon ; ^{sky9999@khu.ac.kr}
• 关键词：Ataxia-telangiectasia ; DNA damage ; Apoptosis ; Premature senescence
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：4 January, 2013
• 年：2013
• 卷：430
• 期：1
• 页码：429-435
• 全文大小：1586 K

文摘

DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-¦Â-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.