Role of Mitochondrial DNA in Cells Exposed to Irradiation : Generation of Reactive Oxygen Species (ROS) is Required for G2 Checkpoint upon Irradiation
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概要
- 論文の詳細を見る
Mitochondria have their own genome encoding subunits of the electron transport chain. Using cells lacking mitochondrial DNA (mtDNA, ρ^0 cells), we studied the role of mtDNA in irradiation. Loss of mtDNA inhibited cell growth and reduced the level of reactive oxygen species (ROS) as compared to ρ^+ cells. ρ^+ cells were more resistant to irradiation than ρ^0 cells. Upon irradiation, ρ^0 cells showed delayed G2 arrest and decreased ability of a cell to recover from the G2 checkpoint compared to ρ^+ cells. Irradiation increased the generation of ROS even more in ρ^+ cells. Irradiation markedly increased the levels of phosphorylated forms of extracellular-regulated kinases, p42 and p44 (ERK1/2) in ρ^+ cells, whereas phosphorylated levels of the kinases were affected slightly in ρ^0 cells. Furthermore, inhibition of the ERK pathway led to a delayed G2 arrest and a delayed recovery from the arrest in irradiated ρ^+ cells, and treatment with NAC also induced dysfunction of the G2 checkpoint in irradiated ρ^+ cells. These results suggest that the accumulation of ROS potentiated ERK1/2 kinases after irradiation in ρ^+ cells, leading to less sensitivity to irradiation. Thus, mtDNA is important for the generation of ROS that act as second messenger.
- 公益社団法人日本薬学会の論文
- 2005-06-01
著者
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AKASHI Makoto
Department of Physics, Hirosaki University
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Akashi Makoto
Department Of Physics Hirosaki University
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HAYAKAWA Kazushige
Department of Radiology and Radiation Oncology, Gunma University School of Medicine
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HAYASHI Junichi
Institute of Biological Sciences, University of Tsukaba.
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Hayakawa Kazushige
北里大学 医学部放射線科学
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Hayakawa Kazushige
Department Of Experiment Radiology Oncology The University Of Texas M. D. Anderson Cancer Center
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Akashi Makoto
Department Of Radiation Emergency Medicine Research Center For Radiation Emergency Medicine National
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WATANABE Keiko
Department of Pathology, Saga Medical School
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Takai Daisaku
Department Of Radiation Emergency Medicine Research Center For Radiation Emergency Medicine National
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Kawamura Saori
Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, Nation
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Kawamura Saori
Department Of Radiology Kitasato University School Of Medicine
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Watanabe Keiko
Department Of Pathology And Biodefense Division Of Cellular And Molecular Pathology Faculty Of Medic
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Hayashi Junichi
Institute Of Biological Sciences University Of Tsukuba:center For Tsukuba Advanced Research Alliance
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Hayashi Junichi
Institute Of Biological Sciences University Of Tsukuba
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Hayashi Junichi
Institute Of Biological Scences University Of Tsukuba
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Watanabe Keiko
Department Of Radiation Emergency Medicine Research Center For Radiation Emergency Medicine National
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Watanabe Keiko
Department Of Aerospace Engineering Graduate School Of Engineering Tohoku University
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