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

Kim,Eun  Ju; Lee,Jeok; Jung,Yu  Ri; Park,Jung-Jin; Park,Myung-Jin; Lee,Jae-Seon; Kim,Chun-Ho; Lee,Yoon-Jin; Lee,Minyoung

doi:10.3892/ijmm.2014.2048

March-2015 Volume 35 Issue 3

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March-2015 Volume 35 Issue 3

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Article

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
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Affiliations: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Division of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea
Pages: 731-738
|
Published online on: December 24, 2014

https://doi.org/10.3892/ijmm.2014.2048
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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