No abstract

SC79 is a novel Akt activator. The current study tested its potential effect against oxygen and glucose deprivation (OGD)/re-oxygenation-induced myocardial cell death. We showed that SC79 activated Akt and protected H9c2 myocardial cells and primary murine myocardiocytes from OGD/re-oxygenation. Reversely, Akt inhibitor MK-2206 or Akt1 shRNA knockdown almost completely abolished SC79-mediated myocardial cytoprotection. SC79 treatment in H9c2 cells inhibited OGD/re-oxygenation-induced programmed necrosis pathway, evidenced by mitochondrial depolarization and cyclophilin D-p53-ANT-1 (adenine nucleotide translocator 1) association. Further, SC79 activated Akt downstream NF-E2-related factor 2 (NRF2) signaling to suppress OGD/re-oxygenation-induced reactive oxygen species (ROS) production. Reversely, NRF2 shRNA knockdown in H9c2 cells largely attenuated SC79-induced ROS scavenging ability and cytoprotection against OGD/re-oxygenation. Together, we conclude that activation of Akt by SC79 protects myocardial cells from OGD/re-oxygenation.

Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to reveal the expression of HMGB 1-mediated signaling pathway and oxidative stress in resveratrol-treated diabetic mice. The significant increase in serum HMGB 1 concentration in diabetic mice was attenuated by treatment with resveratrol. Similarly, western blot analysis revealed a significant increase of HMGB 1 protein in monocytes and heart tissues of diabetic mice, and resveratrol partly normalized the changes. In addition, resveratrol abrogated the increased expression of HMGB 1-mediated signaling pathway, oxidative stress, fibrosis, and inflammation in diabetic hearts. In conclusion, inhibition of HMGB 1-mediated signaling pathway and oxidative stress may contribute to resveratrol-induced anti-inflammatory and antifibrotic effects in DCM.