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AE Pappa, VK Vasiliou; The Cytosolic ALDH3A1 Protects Corneal Epithelium against UV-Induced Toxicity . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1644.
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Purpose: The cytosolic ALDH3A1 is expressed in abundance in mammalian corneal epithelium, representing 20-40% of the total water-soluble protein. Since corneal epithelium is constantly exposed to UV light, it is hypothesized that ALDH3A1 protects the eye from the deleterious effects of UV radiation. Among the proposed roles for the corneal ALDH3A1 is metabolism of UV-induced lipid peroxidation products, (e.g. 4-hydroxy-2-nonenal, 4-HNE), generation of UV-absorbing NADPH, and direct absorption of UV radiation. The aim of this study was to elucidate the biological role of ALDH3A1 against UV and aldehyde toxicity. Methods: Using stable transfection a corneal cell line overexpressing the human ALDH3A1 was generated. The cell line was exposed to various UVB and UVC doses and 4-HNE concentrations. Cell viability and DNA fragmentation assays were performed. Pyridine nucleotide contents were determined. Corneal epithelial cells lacking ALDH3A1 expression were also examined. Results: We observed that corneal epithelial cells overexpressing the human ALDH3A1 exhibited protection against UV- and 4-HNE-induced cytotoxicity as well as UV- and 4-HNE-induced apoptosis. Western blot analysis using an anti-4-HNE/protein adduct antibody revealed that ALDH3A1 also prevents 4-HNE-protein adduct formation. No significant difference was observed in the NADP/NADPH ratio between the cell line expressing the enzyme and the control cell line. Long exposure to UV led to complete inactivation of the enzyme, most likely caused by chemical modification, and thus ALDH3A1 may have a protective role by directly absorbing UV light. Conclusion: These results provide evidence for a significant role of ALDH3A1 in the detoxification of aldehydes produced by UV-induced lipid peroxidation and/or direct absorption of UV light in human corneal epithelium.
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