The function of RNase L and its degradation mechanism in cardiac acute ischemic injury.
Apoptosis
; 25(5-6): 400-411, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32385693
ABSTRACT
RNase L is generally thought to play a key role in antiviral defenses. Although RNase L protein and mRNA are known to be highly expressed in myocardial tissue, there are few studies of the potential functions of RNase L in myocardial tissue. In this study, we tested the hypothesis that RNase L may be involved in the pathological process of cardiac ischemic injury. RNase L-overexpressing and RNase L knockdown H9c2 cell lines were subjected to the oxygen and glucose deprivation (OGD) model, and RNase L knockout mice were subjected to acute myocardial infarction surgical procedures to investigate the function of RNase L in ischemic heart injury. OGD induced abnormal aggregation of double-stranded RNA in H9c2 cells, activated RNase L within 6 h of OGD initiation, and mediated apoptosis via the c-Jun N-terminal kinase pathway. In addition, RNase L knockout mice were more tolerant of myocardial infarction, and this knockout protected heart function and prevented pathological ventricular remodeling. Notably, both in in vivo and in vitro experiments, RNase L was gradually diminished during prolonged ischemic injury, which we speculate is an adaptive protective response serving to reduce myocardial ischemic damage. These results suggest that RNase L plays a role in the pathological process of cardiac acute ischemic injury. It is first activated by ischemic injury, causing cardiomyocyte death, but gradually diminishes to protect the heart from further damage.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Traumatismo por Reperfusão Miocárdica
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Miócitos Cardíacos
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Proteínas Quinases JNK Ativadas por Mitógeno
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Endorribonucleases
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Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Apoptosis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China