title: Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells.
abstract: Despite many studies of the effect of ionizing radiation, biological mechanisms of action might differ greatly depend on dose, dose rate, and cell type. This study was performed to explore the effects of low- and high-dose radiation in human immune cell lines. We examined cell sensitivity after irradiation with 0.05, 0.1, or 2Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1Gy had no effect on cell survival in any tested cell line, with the exception of IM-9 cells, whose viability was transiently increased. However, IM-9 and C1R-sB7 cells were very sensitive to high-dose radiation-induced cell death, whereas Jurkat and JM1 cells showed moderate sensitivity, and THP-1 cells were completely resistant. This radiosensitivity was correlated with basal AKT activation, which is induced by phosphorylation. In radiosensitive IM-9 cells, priming with chronic low-dose irradiation blocked cell death induced by high-dose radiation challenge via inhibition of caspase activation and PARP cleavage. AKT phosphorylation was not altered in IM-9 cells, but ERK phosphorylation was greatly elevated immediately after chronic low-dose irradiation. Taken together, our results suggest that the different responses of normal and tumor cells to low-dose and high-dose radiation depend on AKT activation, which is regulated by protein phosphatase 2 (PP2A). In radiosensitive normal cells lacking basal AKT activity, chronic low-dose radiation increases activation of the ERK pathway, which plays an important role in the adaptive response to radiation, providing a very important insight into understanding the effects of ionizing radiation on health.
authors.affiliation: Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.
authors.forename: Hyung Sun
authors.initials: HS
authors.lastname: Park
authors.affiliation: Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.
authors.forename: Ga Eun
authors.initials: GE
authors.lastname: You
authors.affiliation: Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Yang
authors.affiliation: Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Molecular-Targeted Drug Research Center and Korea Institute for Skin and Clinical Sciences, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Radiological Science, Gachon University, Incheon 21936, Republic of Korea.
authors.forename: Young-Khi
authors.initials: YK
authors.lastname: Lim
authors.affiliation: Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea. Electronic address: synam6660@khnp.co.kr.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance; D013601:T-Lymphocytes / Q000528:radiation effects*
chemical_list: D018797:Cell Cycle Proteins; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: AKT; Apoptosis; ERK; Ionizing radiation; Low-dose