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C.I. Santos Marques, P.C. Pereira; Regulation of ubiquitin proteasome pathway by methlyglyoxal in lens epithelial cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1681.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Methlyglyoxal, a highly reactive dicarbonyl, reacts with proteins to form advanced glycation end products (AGEs) thus contributing to various AGE–associated complications. The ubiquitin–proteasome pathway is a major mechanism for selective degradation of damaged proteins. The main objective of this study is to determine whether exposure of lens epithelial cells to methlyglyoxal disrupts the function of ubiquitin–proteasome pathway by interfering with proteolytic capabilities or by increasing the amount of ubiquitinated substrates. Methods: Human lens epithelial cells are treated with methlyglyoxal at different times and concentrations. The levels of ubiquitin–conjugates are determined by western blot. The chymotrypsin–like activity is assayed in cytosolic extracts using a fluorogenic peptide (LLVY–AMC). Conjugation activity to exogenous substrates is evaluated by the ability of cell lysates to ubiquitinate I–lactalbumin and the ability to degrade endogenous substrates is assayed by following degradation of p53. Results: Treatment of lens epithelial cells with methlyglyoxal increases proteasome activity and the endogenous ubiquitin conjugates. The levels of p53, a characteristic ubiquitin–proteasome substrate, decrease in cells treated with methlyglyoxal. Conclusions: Treatment of cells with methlyglyoxal, increases proteolytic capabilities and ubiquitin conjugation activity. This suggest that methlyglyoxal may regulate ubiquitin–proteasome pathway, presumably by increasing the amount of substrates.
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