Background
Celastrol (Cel) has been corroborated as an anti‐inflammatory and anti‐apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)‐induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG‐stimulated cardiomyocyte injury via regulating the miR‐345‐5p/growth arrest‐specific 6 (Gas6) signaling pathway.
Methods
Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit‐8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase‐polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR‐345‐5p.
Results
The present study confirmed the inhibitory effects of Cel in HG‐induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG‐induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl‐2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG‐triggered repression of Gas6 protein expression, and Gas6 loss‐of‐function accelerated HG‐induced cardiomyocyte apoptosis. HG‐triggered up‐regulation of miR‐345‐5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR‐345‐5p. Transfection with miR‐345‐5p inhibitors restrained HG‐induced release of pro‐inflammatory cytokines and cell apoptosis.
Conclusions
The findings of the present study demonstrate that Cel administration antagonized HG‐induced cardiomyocyte apoptosis and inflammation through up‐regulating Gas6 expression by restraining miR‐345‐5p.
Heart failure (HF) has become one of the severe public health problems. The detailed role of mitochondrial function in HF was still unclear. Benzoylaconine (BAC) is a traditional Chinese medicine, but its role in HF still needs to be explored. In this study, oxygen-glucose deprivation and reperfusion (OGD/R) was executed to mimic the injury of H9C2 cells in HF. The viability of H9C2 cells was assessed
via
MTT assay. OGD/R treatment markedly decreased the viability of H9C2 cells, but BAC treatment evidently increased the viability of OGD/R-treated H9C2 cells. The apoptosis of H9C2 was enhanced by OGD/R treatment but suppressed by BAC treatment. The mitochondrial membrane potential was evaluated
via
JC-1 assay. BAC improved the mitochondrial function and suppressed oxidative stress in OGD/R-treated H9C2 cells. Moreover, Western blot analysis revealed that the protein expression of p-AMPK and PGC-1α were reduced in OGD/R-treated H9C2 cells, which was reversed by BAC. Rescue assays indicated that AMPK attenuation reversed the BAC-mediated protective effect on OGD/R-treated cardiomyocytes. Moreover, BAC alleviated myocardial injury
in vivo
. In a word, BAC modulated the mitochondrial function in OGD/R-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis. The findings might provide support for the application of BAC in the treatment of HF.
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