April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Lipid Peroxidation Products--A New Activator of the Canonical Wnt Pathway
Author Affiliations & Notes
  • T. Zhou
    Cell Biology, Oklahoma Univ Health Science Ctr, Oklahoma City, Oklahoma
  • K. Zhou
    Cell Biology, Oklahoma Univ Health Science Ctr, Oklahoma City, Oklahoma
  • G. Gao
    Cell Biology, Zhongshan Medical School , Sun Yat-sen University, Guangzhou, China
  • J. Ma
    Cell Biology, Oklahoma Univ Health Science Ctr, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  T. Zhou, None; K. Zhou, None; G. Gao, None; J. Ma, None.
  • Footnotes
    Support  NIH grants EY018659, EY012231, EY019309, P20RR024215, a grant from OCAST, and a research award from ADA.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5961. doi:
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      T. Zhou, K. Zhou, G. Gao, J. Ma; Lipid Peroxidation Products--A New Activator of the Canonical Wnt Pathway. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5961.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : We have shown previously that the Wnt signaling pathway plays pathogenic roles in diabetic retinopathy and age-related macular degeneration. The purpose of this study is to investigate the causative role of oxidative stress in the canonical Wnt pathway activation.

Methods: : Cultured ARPE19 cells derived from human RPE and bovine retinal capillary endothelial cells (BRCEC) were treated with a lipid peroxidation product, 4-hydroxynonenal (HNE) and an antioxidant, N-Acetyl-Cysteine (NAC). The activation of the canonical Wnt pathway was measured by TOPFLASH assay, an activity assay for luciferase reporter driven by a promoter with TCF/β-catenin-binding sites and by Western blot analysis of Wnt pathway components and target genes. In vivo, rats with streptozotocin-induced diabetes were treated by NAC in drinking water for 8 weeks. Levels of Wnt pathway components and target genes in the eyecups were measured by Western blot analysis. Oxidative stress in the retina was evaluated by immunostaining of 3-nitrotyrosine, a marker of oxidative stress.

Results: : Levels of phosphorylated and total LRP6, a co-receptor of Wnts and totoal β-catenin, a Wnt effector, were significantly increased by HNE. Similarly, TOPFLASH activity and expression of connected tissue growth factor (CTGF), a Wnt target gene, were also up-regulated by HNE. NAC blocked the Wnt activation induced by HNE, suggesting the Wnt pathway activation was induced by oxidative stress. In diabetic rats, HNE and 3-nitrotyrosine immunosignal were more intensive the retina, compared to that of non-diabetic rats, suggesting an increase in oxidative stress. Retinal levels of total LRP6, β-catenin and CTGF were significantly increased in diabetic rats and reduced by the NAC treatment.

Conclusions: : Lipid peroxidation products activated the canonical Wnt pathway through oxidative stress, which plays an important role in the development of retinal diseases.

Keywords: oxidation/oxidative or free radical damage • diabetic retinopathy • retinal pigment epithelium 

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