Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury.

ABSTRACT: The accumulation of DNA damage induced by oxidative stress is a crucial pathogenic factor of endothelial loss in diabetic vascular complications, but it is still unknown whether aberrant glucose metabolism leads to defective DNA repair and accounts for hyperglycemia-induced endothelial oxidative stress injury. Here, we showed that Foxo1 knockdown alleviated diabetes-associated retinal DNA damage and vascular dysfunction. Mechanistically, FOXO1 knockdown avoided persistent DNA damage and cellular senescence under high glucose in endothelial cells by promoting DNA repair mediated by the MRN (MRE11-RAD50-NBS1 complex)-ATM pathway in response to oxidative stress injury. Moreover, FOXO1 knockdown mediated robust DNA repair by restoring glycolysis capacity under high glucose. During this process

SUBMITTER: Sun D 

PROVIDER: S-EPMC9803794 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature