DJ‑1 alleviates high glucose‑induced endothelial cells injury via PI3K/Akt‑eNOS signaling pathway.

Hyperglycemia mediated endothelial cells (ECs) injury is closely associated with diabetic vascular complications. It was revealed that DJ‑1 possesses cellular protective effects by suppressing oxidative stress. The present study aimed to investigate the beneficial effects of DJ‑1 on high glucose (HG)‑induced human umbilical vein endothelial cell (HUVEC) injury and to elucidate its underlying mechanisms. HUVECs were incubated under 5.5 mM (control group) or 25 mM D‑glucose (HG group) and then transfected with recombinant adenoviral vectors to overexpression of DJ‑1. Cell proliferation and apoptosis were measured using the EdU incorporation assay and flow cytometry with Annexin V-FITC/propidium iodide double staining, respectively. Apoptotic‑related proteins were determined using western blot analysis. Reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) and nitric oxide (NO) levels, the content of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) were measured. Results demonstrated that overexpression of DJ‑1 promoted cell proliferation and inhibited HUVECs apoptosis stimulated by HG. DJ‑1 also suppressed the HG‑induced reduction in the Bcl‑2/Bax ratio and HG activated ROS generation in HUVECs. Furthermore, HG significantly increased the levels of LDH and MDA, and reduced the level of SOD; however, these effects were reversed by Ad‑DJ‑1 transfection. Furthermore, the cellular protective effect of overexpression of DJ‑1 enhanced p‑Akt/Akt ratio, eNOS activation and NO production, and these trends were partially reversed by a phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) inhibitor (LY294002). Taken together, the present study highlighted the involvement of DJ‑1 in HG‑related EC injury and identified that DJ‑1 exerts a cellular protective effect in HUVECs exposed to HG induced oxidative stress via activation of the PI3K/Akt‑eNOS signaling pathway.