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Author Dai, Jiawen ♦ Itahana, Koji ♦ Baskar, Rajamanickam
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANIMAL TISSUES ♦ ANTIGENS ♦ APOPTOSIS ♦ CELL CYCLE ♦ COMPARATIVE EVALUATIONS ♦ DNA DAMAGES ♦ FIBROBLASTS ♦ GLYCOGEN ♦ HALF-LIFE ♦ HUMAN POPULATIONS ♦ IRRADIATION ♦ LUNGS ♦ METABOLISM ♦ PHOSPHORYLATION ♦ PROTEINS ♦ RADIOSENSITIVITY ♦ STRESSES
Abstract Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G{sub 1}/S or G{sub 2}/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G{sub 0}, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its known role in radio-resistance.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-02-27
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 458
Issue Number 1


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