Rg1 protects H9C2 cells from high glucose-/palmitate-induced injury via activation of AKT/GSK-3ß/Nrf2 pathway.
J Cell Mol Med
; 24(14): 8194-8205, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32548942
ABSTRACT
Our previous studies have assessed ginsenoside Rg1 (Rg1)-mediated protection in a type 1 diabetes rat model. To uncover the mechanism through which Rg1 protects against cardiac injury induced by diabetes, we mimicked diabetic conditions by culturing H9C2 cells in high glucose/palmitate. Rg1 had no toxic effect, and it alleviated the high glucose/palmitate damage in a dose-dependent manner, as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release to the culture medium. Rg1 prevented high glucose/palmitate-induced cell apoptosis, assessed using cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Rg1 also reduced high glucose-/palmitate-induced reactive oxygen species formation and increased intracellular antioxidant enzyme activity. We found that Rg1 activates protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3ß) pathway and antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicated by increased phosphorylation of AKT and GSK-3ß, and nuclear translocation of Nrf2. We used phosphatidylinositol-3-kinase inhibitor Ly294002 to block the activation of the AKT/GSK-3ß pathway and found that it partially reversed the protection by Rg1 and decreased Nrf2 pathway activation. The results suggest that Rg1 exerts a protective effect against high glucose and palmitate damage that is partially AKT/GSK-3ß/Nrf2-mediated. Further studies are required to validate these findings using primary cardiomyocytes and animal models of diabetes.
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MEDLINE
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Palmitatos
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Transdução de Sinais
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Substâncias Protetoras
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Ginsenosídeos
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Proteínas Proto-Oncogênicas c-akt
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Fator 2 Relacionado a NF-E2
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Glicogênio Sintase Quinase 3 beta
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Glucose
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En
Ano de publicação:
2020
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Article