Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis.
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.
Song
Young Sook
YS
Department of Life Science, University of Seoul, Dongdaemungu, Jeonnondong 90, Seoul 130-743, Republic of Korea.
Lee
Bo Yun
BY
Hwang
Eun Seong
ES
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena; D002477:Cells / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009153:Mutagens; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D004317:Doxorubicin