title: Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells.
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.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Jeok
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Jung
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Division of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Minyoung
authors.initials: M
authors.lastname: Lee
mesh_terms: D016922:Cellular Senescence / Q000235:genetics* / Q000528:radiation effects*; D015536:Down-Regulation; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000528:radiation effects*; D045265:Natriuretic Peptides / Q000235:genetics; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics*
chemical_list: D045265:Natriuretic Peptides; D017382:Reactive Oxygen Species; D012697:Serine Endopeptidases