Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells

Hyung Sun Park, Ga Eun You, Kwang Hee Yang, Ji Young Kim, Sungkwan An, Jie Young Song, Su Jae Lee, Young Khi Lim, Seon Young Nam

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 2 Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1 Gy 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.

Original languageEnglish
Pages (from-to)653-660
Number of pages8
JournalEuropean Journal of Cell Biology
Volume94
Issue number12
DOIs
StatePublished - 2015 Dec 1

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MAP Kinase Signaling System
Ionizing Radiation
Radiation
Phosphorylation
Cell Line
Cell Survival
Cell Death
Protein Phosphatase 2
Jurkat Cells
Radiation Tolerance
Caspases
Tumor Cell Line
Health

Keywords

  • AKT
  • Apoptosis
  • ERK
  • Ionizing radiation
  • Low-dose

Cite this

Park, Hyung Sun ; You, Ga Eun ; Yang, Kwang Hee ; Kim, Ji Young ; An, Sungkwan ; Song, Jie Young ; Lee, Su Jae ; Lim, Young Khi ; Nam, Seon Young. / Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells. In: European Journal of Cell Biology. 2015 ; Vol. 94, No. 12. pp. 653-660.
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Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells. / Park, Hyung Sun; You, Ga Eun; Yang, Kwang Hee; Kim, Ji Young; An, Sungkwan; Song, Jie Young; Lee, Su Jae; Lim, Young Khi; Nam, Seon Young.

In: European Journal of Cell Biology, Vol. 94, No. 12, 01.12.2015, p. 653-660.

Research output: Contribution to journalArticle

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AU - Park, Hyung Sun

AU - You, Ga Eun

AU - Yang, Kwang Hee

AU - Kim, Ji Young

AU - An, Sungkwan

AU - Song, Jie Young

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AU - Lim, Young Khi

AU - Nam, Seon Young

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AB - 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 2 Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1 Gy 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.

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