Modification of Cytoskeletal Proteins by Lipid-derived Aldehydes in the Lens Epithelial Cells

Oxidative stress has been implicated both in senile and diabetic cataractogenesis and recent evidence suggest that the lipid peroxidation product, 4-hydroxynonenal (HNE) mediates the oxidation-induced toxicity. Using human lens epithelial cells (HLEC) and rat lens we have demonstrated that HNE and oxidants such as Fenton reagent induce opacification in the rat lens and apoptosis in HLEC and lens epithelium with a concommitant formation of protein-HNE adducts and disruption of the cytoskeleton. Vimentin and actin were the major cytoskeletal proteins to be degraded by these agents. Tubulin on the other hand was resistant to degradation and displayed a compensatory increase in expression. Our studies suggest that under oxidative stress antioxidants/ HNE-scavengers could ameliorate the formation of protein-HNE adducts, stabilize the lens cytoskeleton and thus prevent cataractogenesis.