Inhibition of brain-type glycogen phosphorylase ameliorates high glucose-induced cardiomyocyte apoptosis via Akt-HIF-1α activation.
Biochem Cell Biol
; 98(4): 458-465, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-31905009
ABSTRACT
Brain-type glycogen phosphorylase (pygb) is one of the rate-limiting enzymes in glycogenolysis that plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Here we investigated the role of pygb in high-glucose (HG)-induced cardiomyocyte apoptosis and explored the underlying mechanisms, by using the specific pygb inhibitors or pygb siRNA. Our results show that inhibition of pygb significantly attenuates cell apoptosis and oxidative stress induced by HG in H9c2 cardiomyocytes. Inhibition of pygb improved glucose metabolism in cardiacmyocytes, as evidenced by increased glycogen content, glucose consumption, and glucose transport. Mechanistically, pygb inhibition activates the Akt-GSK-3ß signaling pathway and suppresses the activation of NF-κB in H9c2 cells exposed to HG. Additionally, pygb inhibition promotes the expression and the translocation of hypoxia-inducible factor-1α (HIF-1α) after HG stimulation. However, the changes in glucose metabolism and HIF-1α activation mediated by pygb inhibition are significantly reversed in the presence of the Akt inhibitor MK2206. In conclusion, this study found that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via activation of Akt-HIF-α.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Doenças Cardiovasculares
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Apoptose
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Glicogênio Fosforilase
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Miócitos Cardíacos
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Diabetes Mellitus Tipo 2
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Glucose
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article