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The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h. H9c2 cells were also incubated with 25 µM resveratrol in the presence of chloroquine (50 µM). Cell viability was determined using an MTT cell survival assay. Cytotoxicity was determined by quantification of the release of lactate dehydrogenase. The expression of Cx43, autophagic maker proteins [Beclin‑1, p62 and microtubule‑associated protein 1 light chain 3 (LC3)], apoptosis maker proteins (B‑cell lymphoma‑2 and Bcl‑2 associated X protein), AMP‑activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were determined using western blotting. Resveratrol treatment led to reduced Cx43 expression levels compared with the 25 mM glucose treatment and significantly reduced the expression of apoptosis‑associated proteins in H9c2 cells under hyperglycemic conditions. Autophagy was increased as indicated by the upregulation of Beclin‑1 and p62 expression and the reduced LC3‑II/LC3‑I ratio. AMPK expression was increased, whereas mTOR expression was reduced in the resveratrol treatment groups. Treatment with chloroquine reversed effect of resveratrol. In conclusion, administration resveratrol may protect H9c2 cells against hyperglycemia‑induced Cx43 upregulation and apoptosis, which may be mediated through the induction of the autophagy signaling pathway.

molecular medicine reports

Upregulation of connexin 43 and apoptosis-associated protein expression by high glucose in H9c2 cells was improved by resveratrol via the autophagy signaling pathway