FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition

Li, Shenping; Deng, Junjie; Sun, Dandan; Chen, Shimei; Yao, Xieyi; Wang, Ning; Zhang, Jian; Gu, Qing; Zhang, Shuchang; Wang, Jing; Zhu, Shaopin; Zhu, Hong; Li, Huiming; Xu, Xun; Wei, Fang

doi:10.1016/j.redox.2022.102530

Cited by 39 publications

(14 citation statements)

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“…To date, studies on impaired DNA repair in diabetes feature extensive analyses of DNA damage markers and the genetic polymorphisms and gene expression of DNA damage repair enzymes [ [11] , [12] , [13] , [14] ] but lack research on specific mechanisms. Our previous study [ 15 ] has revealed that defective DNA repair leads to the accumulation of DNA damage together with oxidative stress during the loss of diabetic ECs. Here, we further explored the molecular mechanisms of DNA repair impairment from the metabolic perspective as diabetes is a metabolic disease.…”

Section: Introductionmentioning

confidence: 99%

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

Sun¹,

Chen²,

Li³

et al. 2023

Redox Biology

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Section: Introductionmentioning

confidence: 99%

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

Sun¹,

Chen²,

Li³

et al. 2023

Redox Biology

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“…FBXW7 was reported to be associated with DR, which in detail, in mouse experiments, silencing FBXW7 enhanced angiogenesis and overexpressing FBXW7 depressed angiogenesis in retinal tissue (Hu et al 2020). Another study showed that the abundant mobilization of DNA damage repair mediated by FBXW7 leads to the downregulation of poly-ADP-ribose-polymerase(PARP) expression and activity in both human endothelial cells and diabetic rat retinas, where RARP plays important roles in endothelial cell impairment in the pathogenesis of diabetic vascular diseases (Li et al 2022). The GeneMANIA (https://genemania.org/) shows that FBXW7 and EYA2 , NTNG1 had directly genetic interactions, with MPDZ had indirectly genetic interaction in Fig.…”

Section: Discussionmentioning

confidence: 99%

Multiple genome-wide association studies of type 2 diabetes implicate several genes are associated with diabetic retinopathy based on UK Biobank

Cai,

Pan,

Tao

et al. 2023

Preprint

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PurposeTo identify the genetic variants associated with diabetic retinopathy in type 2 patients from the UK Biobank cohort (n= 17,015) and supporting replication cohorts GODARTS (n= 5,013), GOSHARE (n= 1,754), Caucasian Australians (n= 518), FinnGen (n= 206,664) and Chinese (n = 1,007).MethodsTotally eleven genome-wide association studies were applied to search for significant genetic variants.ResultsWe found 5 different loci associated with type 2 diabetic retinopathy in or nearest geneEYA2,MPDZ,NTNG1,CTAGE14PandMREGP1. In the primary GWAS, a significant SNP rs6066146 located in geneEYA2showed apvalue of 4.21 × 10−8and may play a role in the development of the disease, with “spleen” reaching a significant level produced by tissue expression analysis. Corresponding heritability of DR was estimated to be 26.73% by SumHer. Among five genes, we found that genesEYA2,MPDZ,NTNG1had genetic interactions and may affect the complex development of retinal blood vessels.ConclusionDiabetic retinopathy is a complication of diabetes that affects the eyes. It is highly likely to occur when high blood sugar damages the retinal blood vessels. There is limited awareness regarding the pathogenesis of DR. Our study identified multiple loci associated with diabetic retinopathy, which may lead to personalized treatments to reduce the burden of the disease.

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“…Long-term hyperglycemia causes abnormal glucose metabolism in the retina and glucose influx into the glycolytic bypass [ 80 ], which leads to increased production of ROS as well as oxidative stress damage in ECs. This process is the main mechanism of DR, and targeting glucose metabolism is also a significant treatment for coping with oxidative stress.…”

Section: Metabolic Pattern Of Retinamentioning

confidence: 99%

PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies

Liu,

Sun,

Zhang

et al. 2024

Cell Biosci

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Background Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. Main body In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. Conclusion Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.

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FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition

Cited by 39 publications

References 70 publications

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

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

Multiple genome-wide association studies of type 2 diabetes implicate several genes are associated with diabetic retinopathy based on UK Biobank

PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies

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