Kinetics of the cell biological changes occurring in the progression of DNA damage-induced senescence |
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Authors: | Sohee Cho Jihoon Park Eun Seong Hwang |
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Institution: | (1) Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong 90, Seoul, 130-743, Republic of Korea;(2) Department of Biochemistry, School of Medicine and Department of Molecular Science & Technology, The Graduate School, Ajou University, Suwon, 443-721, Republic of Korea |
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Abstract: | Cellular senescence is characterized by cell-cycle arrest accompanied by various cell biological changes. Although these changes
have been heavily relied on as senescence markers in numerous studies on senescence and its intervention, their underlying
mechanisms and relationship to each other are poorly understood. Furthermore, the depth and the reversibility of those changes
have not been addressed previously. Using flow cytometry coupled with confocal microscopy and Western blotting, we quantified
various senescence-associated cellular changes and determined their time course profiles in MCF-7 cells undergoing DNA damage-induced
senescence. The examined properties changed with several different kinetics patterns. Autofluorescence, side scattering, and
the mitochondria content increased progressively and linearly. Cell volume, lysosome content, and reactive oxygen species
(ROS) level increased abruptly at an early stage. Meanwhile, senescence associated β-galactosidase activity increased after
a lag of a few days. In addition, during the senescence progression, lysosomes exhibited a loss of integrity, which may have
been associated with the accumulation of ROS. The finding that various senescence phenotypes matured at different rates with
different lag times suggests multiple independent mechanisms controlling the expression of senescence phenotypes. This type
of kinetics study would promote the understanding of how cells become fully senescent and facilitate the screening of methods
that intervene in cellular senescence. |
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Keywords: | lipofuscin lysosome mitochondria ROS SA β-Gal senescence phenotype |
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