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C. I. Marques, P. Pereira; HNE Induces HO-1 Expression in RPE Cells Through the Activation of p38 MAPK. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1850.
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Development of age-related macular degeneration (AMD) is associated with functional abnormalities and cell death in retinal pigment epithelial (RPE) cells attributable in part oxidative stress. Recent studies showed alterations in expression of retinal heme oxygenase-1 (HO-1) in response to various forms of stress. 4-hydroxynonenal (4-HNE) is a major lipid peroxidation product in the RPE, and forms adducts with proteins disrupting critical cell functions. The purpose of the study is to investigate the role of HO-1 in detoxification of HNE, thus ensuring cell survival in the RPE. The signal pathways involved in up-regulation of HO-1 were also investigated.
Cultured RPE cells (ARPE-19 cells) were treated with 4-HNE. Specific pharmacologic inhibitors against MAPK were used to investigate the signalling cascade involved in regulation of HO-1. Cell viability was assessed by MTT. The levels of HO-1 and p38 phosphorylation were determined by western blotting. The HO-1 activity was also evaluated by measuring the formation of bilirubin. Proteasome activity was determined using fluorogenic peptides as substrates.
Treatment with 4-HNE increased HO-1 activity and HO-1 expression in a dose-dependent manner in cultured RPE cells. The HNE-induced overexpression of HO-1 is reverted upon treatment with p38 MAPK inhibitors.
4-HNE-induced overexpression of HO-1 in the RPE is dependent on p38 MAPK, and is an important component for cell response and survival to oxidative damage.
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