Study On Roles Of SIRT3 And SENP1 In Microvascular Pathology Of Diabetic Retinopathy

Diabetic retinopathy is the leading cause of loss of vision in the working population in diabetic complications and a key role is played by microvascular pathology.Many studies focus on the transcriptional level of proteins,but few studies of the protein post-translational modification is carried out.Our study is based on the latest studies of diabetic retinopathy and protein post-translational modification and clarify the effect of post-translational regulation dependent on SIRT3 and SENP1 in microvascular pathology ofdiabetic retinopathy.First,we found that a high concentration of glucose inhibited the expression of the deacetylase SIRT3,which resulted in a reduction in MnSOD activity in bovine retinal capillary endothelial cells and in the retinas of diabetic rats.Conversely,SIRT3 overexpression attenuated hyperglycemic stress through deacetylation and activation of MnSOD.Furthermore,the hyperglycemia-induced downregulation of SIRT3 involved the activation of poly(ADP-ribose)polymerase(PARP).Our study is the first to link the deacetylation of MnSOD by PARP-regulated SIRT3 with the pathogenesis of diabetic retinopathy.Second,We demonstrated that a high concentration of glucose inhibited the expression of the Sentrin/SUMO-specific protease 1(SENP1),which resulted in an increase in DBC1 sumoylation in bovine retinal pericytes(BRPCs).Furthermore,SENP1 overexpression attenuated hyperemia-induced apoptosis of BPRCs.We also provide evidence that DBC1 sumoylation/desumoylation is involved in the SENP1-regulated apoptosis of BRPCsunder high-glucose conditions.Understanding the role of SIRT3 and SENP1 in the pathogenesis of diabetic retinopathy could help elucidate key molecular targets for future pharmacological interventions.