MicroRNA-503 regulates hypoxia-induced cardiomyocytes apoptosis through PI3K/Akt pathway by targeting IGF-1R.
Biochem Biophys Res Commun
; 506(4): 1026-1031, 2018 12 02.
Article
em En
| MEDLINE
| ID: mdl-30404731
ABSTRACT
Coronary heart disease is the second highest specific cause of death. H9c2 cardiomyocytes were subjected to hypoxia (1% O2) for 0, 6, 12, 24 and 48â¯h. Cell apoptosis and the activity of caspase3/7 was detected using ELISA; western blot was applied to determine the cleaved-caspase3 (c-caspase3), cleaved-PARP (c-PARP) and cytochrome C (Cyto C) expression after the inhibitor negative control (in-NC), miR-503 inhibitor, mimic negative control (mi-NC) and miR-503 mimic were transfected into cells for 48â¯h. Moreover, flow cytometry was applied to evaluate mitochondrial membrane potential. In addition, luciferase reporter gene assay was used for detection the relationship between miR-503 and insulin-like growth-factor-1 receptor (IGF-1R). Real-time PCR showed microRNA-503 (miR-503) was elevated in a time-dependent manner under hypoxia. MiR-503 inhibition prevented cell apoptosis and reduced caspase3/7 activity and the expression of c-caspase3 and c-PARP, prevented mitochondrial membrane potential collapse and reduced the cyto C level in cytosol. While, miR-503 overexpression showed a pro-apoptotic role and resulted in mitochondrial membrane potential loss. MiR-503 directly targets IGF-1R in H9c2 cardiomyocytes. The depletion of IGF-1R using a specific IGF-1R siRNA (siIGF-1R) abolished anti-apoptotic function of miR-503 inhibitor, and LY294002 showed a similar trend. In summary, miR-503 promoted cell apoptosis, caused mitochondrial membrane potential collapse and the emancipation of cyto C from mitochondrial through PI3K/Akt pathway via targeting IGF-1R in H9c2 cardiomyocytes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Receptor IGF Tipo 1
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Apoptose
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Fosfatidilinositol 3-Quinases
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Miócitos Cardíacos
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MicroRNAs
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2018
Tipo de documento:
Article