title: Roles for redox signaling by NADPH oxidase in hyperglycemia-induced heme oxygenase-1 expression in the diabetic retina.
abstract: OBJECTIVE
  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.
authors: Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors: Meihua
authors: M
authors: He
authors: Hong
authors: H
authors: Pan
authors: Chunxia
authors: C
authors: Xiao
authors: Mingliang
authors: M
authors: Pu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D061745:Antioxidant Response Elements; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000201:enzymology*; D019084:Fluorescent Antibody Technique, Indirect; D005947:Glucose / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006943:Hyperglycemia / Q000201:enzymology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C556060:6,7-dihydro-5H-pyrrolo(1,2-a)imidazole; D000098:Acetophenones; D007093:Imidazoles; D008562:Membrane Glycoproteins; D011758:Pyrroles; D017382:Reactive Oxygen Species; C056165:acetovanillone; D051547:Heme Oxygenase-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D005947:Glucose
keywords: NADPH oxidase; antioxidant response element; db/db mouse; diabetic retina; heme oxygenase-1