Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis
Young Sook Song1, Bo Yun Lee, Eun Seong Hwang
1Department of Life Science, University of Seoul, Dongdaemungu, Jeonnondong 90, Seoul 130-743, Republic of Korea.
Abstract:
Cellular senescence and apoptosis are both caused by DNA damage stresses, and their severity appears to decide between the two cellular outcomes. In recent studies, it is suggested that these two states may be closely linked and be switched by certain molecular determinants such as p21WAF1 and caspase (Abdelhadi, 2003). However, it is unknown how the pathways to senescence and apoptosis are determined. In addition, although DNA damage stresses frequently accompany cellular accumulation of reactive oxygen species (ROS), how ROS are involved in the decision between the two pathways is unknown. In the present study, MCF-7 cells were induced to senescence or apoptosis by the treatment of varying doses of adriamycin. And, through a series of time course studies, ROS generation profiles and changes in the status of the proteins involved in growth regulation and apoptosis were determined. Significant levels of ROS were produced in senescing cells but not in apoptotic cells. Therefore, senescence is associated with ROS accumulation, but apoptosis is caused independently of ROS. In addition, cells in these two states exhibited quite distinct time course profiles of the proteins, p53, p21WAF1, and E2F1.
Insights
Cellular senescence involves reactive oxygen species (ROS) accumulation, while apoptosis occurs independently of ROS. These distinct pathways are influenced by DNA damage severity and molecular determinants.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cellular senescence and apoptosis are critical outcomes of DNA damage.
- The decision between senescence and apoptosis is influenced by damage severity and molecular factors like p21WAF1 and caspase.
- The role of reactive oxygen species (ROS) in determining these cellular fates remains unclear.
Purpose of the Study:
- To investigate the involvement of ROS in the differential pathways of cellular senescence and apoptosis.
- To analyze the distinct molecular profiles associated with senescence versus apoptosis following DNA damage.
Main Methods:
- MCF-7 cells were treated with varying doses of adriamycin to induce senescence or apoptosis.
- Time-course studies were conducted to monitor ROS generation and protein expression levels.
- Key proteins including p53, p21WAF1, and E2F1 were analyzed.
Main Results:
- Senescing cells exhibited significant ROS production, whereas apoptotic cells did not.
- Apoptosis proceeded independently of ROS accumulation.
- Distinct temporal expression patterns of p53, p21WAF1, and E2F1 were observed in senescing versus apoptotic cells.
Conclusions:
- Cellular senescence is associated with ROS accumulation, distinguishing it from apoptosis.
- Apoptosis can be triggered independently of ROS.
- DNA damage response pathways leading to senescence and apoptosis are differentially regulated, involving distinct molecular players and ROS involvement.
