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|Roles for Redox Signaling by NADPH Oxidase in Hyperglycemia-Induced Heme Oxygenase-1 Expression in the Diabetic Retina|
|He, Meihua1,2,3; Pan, Hong1,2,3; Xiao, Chunxia1; Pu, Mingliang1,2,3|
|关键词||Antioxidant Response Element Heme Oxygenase-1 Nadph Oxidase Diabetic Retina Db/db Mouse|
|刊名||INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE|
|WOS标题词||Science & Technology|
|关键词[WOS]||ANTIOXIDANT GENE-EXPRESSION ; PIGMENT EPITHELIAL-CELLS ; OXIDATIVE STRESS ; DB/DB MICE ; ISCHEMIA/REPERFUSION INJURY ; ENDOTHELIAL-CELLS ; HYDROGEN-PEROXIDE ; BARRIER BREAKDOWN ; PROTECTIVE ROLE ; RETINOPATHY|
PURPOSE. The antioxidant response element (ARE)-mediated antioxidant pathway has an important role in maintaining the redox status of the retina. The expression of ARE-mediated antioxidants, such as heme oxygenase-1 (HO-1), remains unclear in the db/db mice. We evaluated the expression of HO-1 in the retinas of db/db mice and investigated a possible role for NADPH oxidase.
METHODS. Fresh retinas were harvested from 8-, 12-, and 20-week db/db or db/m mice. Reactive oxygen species were detected by dihydroethidium. The expression levels of HO-1, Nox2, and Nox4 were evaluated by immunohistochemistry and Western blotting. In vitro retina explants culture was used to assess the role of NADPH oxidase in high glucose-induced HO-1 expression.
RESULTS. The expression of HO-1 was increased in the retinas of 8-week db/db mice, while it was decreased in 20-week db/db mice compared to age-matched controls. Similarly, the activation of Nox4 was increased in the retinas at 8 weeks and returned to basal levels at 20 weeks in db/db mice compared to age-matched controls. The activation of Nox2 was increased in the retinas of 8-, 12-, and 20-week db/db mice compared to age-matched controls. The NADPH oxidase inhibitors apocynin and DPI significantly blocked the HO-1 expression that was induced by high glucose levels in cultured retina explants.
CONCLUSIONS. The expression patterns of HO-1, Nox2, Nox4 in db/db mouse retinas, and the suppressive effects of NADPH oxidase inhibitors on the expression of HO-1 induced by high glucose levels in cultured retina explants suggest that the expression of HO-1 is, at least partially, mediated by NADPH oxidase in this diabetic animal model.
|项目编号||2009CB320900 ; 2011CB510206 ; 30831160516 ; 81200691 ; 20090001120075|
|资助机构||National Basic Research Program of China (973 Program) ; National Science Foundation of China ; Ministry of Education of China|
|作者单位||1.Peking Univ, Sch Basic Med Sci, Dept Anat & Embryol, Beijing 100083, Peoples R China|
2.Peking Univ, Minist Educ, Key Lab Machine Percept, Beijing 100083, Peoples R China
3.Peking Univ, Minist Educ, Key Lab Visual Impairment & Restorat, Beijing 100083, Peoples R China
|He, Meihua,Pan, Hong,Xiao, Chunxia,et al. Roles for Redox Signaling by NADPH Oxidase in Hyperglycemia-Induced Heme Oxygenase-1 Expression in the Diabetic Retina[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2013,54(6):4092-4101.|
|APA||He, Meihua,Pan, Hong,Xiao, Chunxia,&Pu, Mingliang.(2013).Roles for Redox Signaling by NADPH Oxidase in Hyperglycemia-Induced Heme Oxygenase-1 Expression in the Diabetic Retina.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,54(6),4092-4101.|
|MLA||He, Meihua,et al."Roles for Redox Signaling by NADPH Oxidase in Hyperglycemia-Induced Heme Oxygenase-1 Expression in the Diabetic Retina".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 54.6(2013):4092-4101.|
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