Involvement of corin downregulation in ionizing radiation-induced senescence of myocardial cells.
Int J Mol Med
; 35(3): 731-8, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25543718
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 ß-galactosidase (SA-ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
/
Serina Endopeptidases
/
Expressão Gênica
/
Senescência Celular
/
Miócitos Cardíacos
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2015
Tipo de documento:
Article