Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells

  • Authors:
    • Eun Ju Kim
    • Jeok Lee
    • Yu Ri Jung
    • Jung-Jin Park
    • Myung-Jin Park
    • Jae-Seon Lee
    • Chun-Ho Kim
    • Yoon-Jin Lee
    • Minyoung Lee
  • View Affiliations

  • Published online on: December 24, 2014     https://doi.org/10.3892/ijmm.2014.2048
  • Pages: 731-738
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Abstract

Radiation-induced heart disease (RIHD) is becoming an increasing concern for patients and clinicians alike due to the use of radiotherapy for the treatment of breast cancer, Hodgkin's lymphoma, pediatric cancer and tumors of the thorax. However, the mechanisms underlying this phenomenon remain largely unknown. As the senescent cell fraction following irradiation is known to increase, in the present study, we investigated whether ionizing radiation (IR) causes the onset of heart disease by inducing cellular senescence in cardiomyocytes. In the present study, we evaluated the effects of IR on HL-1 and H9C2 cells, cells predominantly used in in vitro myocardial cell models. We found that the exposure of the HL-1 and H9C2 cells to IR induced reactive oxygen species (ROS)-mediated cellular senescence, as shown by staining of senescence-associated β-galactosidase (SA-β-gal). The levels of ROS in irradiated cells were determined using the fluorescent dye, 2', 7'-dichlorodihydrofluorescein diacetate (DCF-DA). Notably, the expression of corin, a cardiac protease that is essential for the proteolytic cleavage of natriuretic peptides, was significantly decreased following the exposure of the cells to IR. Importantly, the knockdown of corin by RNA interference enhanced IR-induced senescence. On the contrary, the overexpression of natriuretic peptides reversed the IR-induced senescence. Taken together, our data suggest that defects in corin function and the inhibition of natriuretic peptides following exposure to IR may contribute to the development of RIHD through the acceleration of cellular senescence.
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March-2015
Volume 35 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kim EJ, Lee J, Jung YR, Park J, Park M, Lee J, Kim C, Lee Y and Lee M: Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells. Int J Mol Med 35: 731-738, 2015
APA
Kim, E.J., Lee, J., Jung, Y.R., Park, J., Park, M., Lee, J. ... Lee, M. (2015). Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells. International Journal of Molecular Medicine, 35, 731-738. https://doi.org/10.3892/ijmm.2014.2048
MLA
Kim, E. J., Lee, J., Jung, Y. R., Park, J., Park, M., Lee, J., Kim, C., Lee, Y., Lee, M."Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells". International Journal of Molecular Medicine 35.3 (2015): 731-738.
Chicago
Kim, E. J., Lee, J., Jung, Y. R., Park, J., Park, M., Lee, J., Kim, C., Lee, Y., Lee, M."Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells". International Journal of Molecular Medicine 35, no. 3 (2015): 731-738. https://doi.org/10.3892/ijmm.2014.2048