Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic postconditioning.
Heart Lung Circ
; 23(2): 152-8, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-23948289
ABSTRACT
AIM:
Recent studies have demonstrated that Notch signalling pathway is an important mediator of cardiac repair and regeneration after myocardial infarction. However, the mechanism by which Notch signalling pathway is mediating cardioprotection after ischaemic postconditioning (IPost) is still not understood thoroughly. The aim of the present study was to investigate the mechanism by which Notch signalling pathway mediated the cardioprotection effect after IPost.METHODS:
Rat heart-derived H9c2 cells were randomly divided into six groups as follows Control group, hypoxia/reoxygenation group (H/R), H/R+N1ICD group, H-post group, H-post+Notch-1miRNA group, and Mock group. We used pcDNA3.1-Myc-His plasmid and RNA interference (RNAi) to activate/inhibit the expression of Notch-1 in H9c2 cell lines. The Bcl-2, Bax genes and proteins were assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. The effects of Notch 1 signalling on cell survival, proliferation and apoptosis were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and flow cytometry analysis, respectively. Furthermore, Notch 1 signalling induced the disruption of mitochondrial membrane potential, thus leading to the activation of caspase-9/-3 measured using the colorimetric activity assay.RESULTS:
We found Notch 1 signalling reduced cardiomyocyte apoptosis in IPost through regulating the expression of Bcl-2, Bax and activation of caspase-9 and -3. We found that after transfected with pcDNA3.1-Myc-His plasmid, activation of the Notch 1 gene effectively promoted cell proliferation and inhibited apoptosis. The Notch 1 upregulation was accompanied by an upregulation of Bcl-2 and a downregulation of Bax. In addition, a paralled increase in caspase-9/-3 activities was observed. These effects were blunted by transfected with Notch-1 miRNA in the H9c2 cells.CONCLUSION:
Notch 1 signalling has a cardioprotection effect, which may result from cardiomyocyte apoptosis, by means of regulating the expression of cell apoptosis inhibiting proteins Bcl-2, Bax and the activation of caspase-9 and -3.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Apoptose
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Precondicionamento Isquêmico Miocárdico
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Miócitos Cardíacos
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Receptor Notch1
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article