title: Deacetylation of MnSOD by PARP-regulated SIRT3 protects retinal capillary endothelial cells from hyperglycemia-induced damage.
abstract: A key initiator in the development of diabetic retinopathy is considered to be the production of reactive oxygen species (ROS) in the retinal mitochondria, and their scavenging enzyme, manganese superoxide dismutase (MnSOD), is compromised. However, the mechanism by which high glucose regulates MnSOD is unclear. In this study, we found that a high concentration of glucose inhibited the expression of the histone 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. Understanding the role of SIRT3 in the pathogenesis of diabetic retinopathy could help elucidate key molecular targets for future pharmacological interventions.
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, China. Electronic address: drxuxun@sjtu.edu.cn.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
mesh_terms: D000107:Acetylation; D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D056566:Sirtuin 3 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; D056566:Sirtuin 3; D005947:Glucose
keywords: Diabetic retinopathy; MnSOD; PARP; Reactive oxygen species; SIRT3