Obtusifolin inhibits high glucose­induced mitochondrial apoptosis in human umbilical vein endothelial cells.

DM is often accompanied by macrovascular complications. Obtusifolin, which is an anthraquinone­based compound with antioxidant activity, is obtained from the seeds of Cassia obtusifolia. In this study, the potential effect of obtusifolin was investigated in human umbilical vein endothelial cells. The results from flow cytometry analysis revealed that pretreatment with obtusifolin depressed the production of cellular reactive oxygen species that was induced by high glucose content. Moreover, the results showed that pretreatment with obtusifolin reduced the level of malondialdehyde, as well as recovered the activities of mitochondrial complex I/III, catalase and superoxide dismutase. Furthermore, flow cytometry analysis also revealed that mitochondrial membrane potential and cell apoptosis were recovered, and inhibited by obtusifolin, respectively. The expression of X chromosome­linked IAP was upregulated, whereas the expressions of poly ADP­ribose polymerase and cysteinyl aspartate specific proteinase­3/9 were downregulated by the pretreatment with obtusifolin. Notably, the western blot analyses showed that the release of Omi/HtrA2 into the cytosol was prevented by the pretreatment with obtusifolin. Conclusively, it was suggested that obtusifolin may provide protection against mitochondrial apoptosis largely through inhibition of the release of Omi/HtrA2 from mitochondria into cytosol.

Upregulation of Periostin Prevents High Glucose-Induced Mitochondrial Apoptosis in Human Umbilical Vein Endothelial Cells via Activation of Nrf2/HO-1 Signaling.

BACKGROUND/AIMS: High glucose-induced oxidative damage to endothelial cells plays a central role in the pathogenesis of diabetic vascular complications. This study was undertaken to explore the role of periostin in high glucose-induced endothelial cell apoptosis and associated molecular mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (33.3 mmol/L) and examined for the expression of periostin. The effects of periostin upregulation on high glucose-induced apoptosis, mitochondrial dysfunction, and reactive oxygen species (ROS) production were determined. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) by periostin was checked. HO-1 knockdown experiments were done to confirm its role in the action of periostin in high glucose-exposed HUVECs. RESULTS: High glucose significantly upregulated the expression of periostin in HUVECs. Enforced expression of periostin attenuated high glucose-induced apoptosis in HUVECs, as determined by TUNEL staining and caspase-3 activity assay. Periostin overexpression prevented loss of x0394;x03C8;m, release of mitochondrial cytochrome c, and dysregulation of Bcl-2 and Bax in high glucose-exposed HUVECs. Periostin upregulation suppressed high glucose-induced ROS generation and activated the Nrf2/HO-1 signaling. HO-1 silencing restored high glucose-induced ROS generation and apoptotic response in periostin-overexpressing HUVECs. CONCLUSION: Periostin mitigates high glucose-induced mitochondrial apoptosis in endothelial cells, via activation of Nrf2/HO-1 signaling and reduction of ROS formation. Further studies are warranted to explore the therapeutic potential of periostin in diabetic vascular complications.