5-aza-2'-deoxycytidine in the regulation of antioxidant enzymes in retinal endothelial cells and rat diabetic retina  

作　　者：Man-Yun Xie Yan Yang Ping Liu Yan Luo Shi-Bo Tang 

机构地区：[1]Department of Ophthalmology,the Second Xiangya Hospital,Central South University [2]Hunan Clinical Research Center of Ophthalmic Diseas [3]The State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University [4]Aier School of Ophthalmology,Central South University [5]Aier Research Institute of Ophthalmology

出　　处：《International Journal of Ophthalmology(English edition)》2019年第1期1-7,共7页国际眼科杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China (No.81600757);Department of Science and Technology, Hunan (No.2015TP2007)

摘　　要：AIM: To investigate the roles of a DNA methyltransferase(DNMT) inhibitor 5-aza-2'-deoxycytidine(5-aza-dC) in the regulation of antioxidant enzymes in diabetic retinopathy(DR) models. METHODS: DNMTs expressions and activity, and changes of two key antioxidant enzymes in DR, MnSOD(encoded by SOD2 gene) and glutathione S-transferase theta 1(GSTT1), were quantified in the isolated human retinal endothelial cells(HRECs) exposed to high glucose(HG) with or without 5-aza-dC treatment. The downstream exacerbating factors including vascular endothelial growth factor(VEGF), intercellular adhesion molecule 1(ICAM-1) and matrix metalloproteinase 2(MMP2), which are implicated in the pathogenesis of DR and closely related to oxidative stress were also analyzed. The key parameters were confirmed in the retina from streptozotocin(STZ) diabetic rats. RESULTS: DNMTs expression and DNMT activity was induced in HRECs exposed to HG. Hyperglycemia decreased MnSOD and GSTT1 expression. 5-aza-dC administration effectively suppressed DNMTs expression and activity and reversed the MnSOD and GSTT1 expression under HG condition. VEGF, ICAM-1 and MMP2 induced by HG were also suppressed by 5-aza-dC treatment. Similar results were observed in the retina from STZ diabetic rats. CONCLUSION: Our findings suggest that DNA methylation may serves as one of the mechanisms of antioxidant defense system disruption in DR progression. Modulation of DNA methylation using pharmaceutic means such as DNMT inhibitors could help maintain redox homeostasis and prevent further progression of DR.AIM: To investigate the roles of a DNA methyltransferase(DNMT) inhibitor 5-aza-2'-deoxycytidine(5-aza-dC) in the regulation of antioxidant enzymes in diabetic retinopathy(DR) models.METHODS: DNMTs expressions and activity, and changes of two key antioxidant enzymes in DR, MnSOD(encoded by SOD2 gene) and glutathione S-transferase theta 1(GSTT1), were quantified in the isolated human retinal endothelial cells(HRECs) exposed to high glucose(HG) with or without 5-aza-dC treatment. The downstream exacerbating factors including vascular endothelial growth factor(VEGF), intercellular adhesion molecule 1(ICAM-1) and matrix metalloproteinase 2(MMP2), which are implicated in the pathogenesis of DR and closely related to oxidative stress were also analyzed. The key parameters were confirmed in the retina from streptozotocin(STZ) diabetic rats.RESULTS: DNMTs expression and DNMT activity was induced in HRECs exposed to HG. Hyperglycemia decreased MnSOD and GSTT1 expression. 5-aza-dC administration effectively suppressed DNMTs expression and activity and reversed the MnSOD and GSTT1 expression under HG condition. VEGF, ICAM-1 and MMP2 induced by HG were also suppressed by 5-aza-dC treatment. Similar results were observed in the retina from STZ diabetic rats.CONCLUSION: Our findings suggest that DNA methylation may serves as one of the mechanisms of antioxidant defense system disruption in DR progression. Modulation of DNA methylation using pharmaceutic means such as DNMT inhibitors could help maintain redox homeostasis and prevent further progression of DR.

关 键 词：DNA methylation diabetic model 5-AZA-DC oxidative stress inflammation human RETINAL endothelial cells RAT 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]