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R. F. Jacob, Y. Self-Medlin, M. D. Aleo, C. M. Doshna, R. P. Mason; 1,2-Naphthoquinone Stimulates Lipid Peroxidation and Cholesterol Domain Formation in Model Membranes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2088.
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© ARVO (1962-2015); The Authors (2016-present)
Naphthalene has been shown to induce cataract development through the formation of its reactive metabolite, 1,2-naphthoquinone (NQ), and subsequent production of reactive oxygen species, in the ocular lens. NQ increases lens protein oxidation and disrupts fiber cell membrane function; however, the association of these effects with changes in membrane structure is not understood. The goal of this study was to determine the direct effects of NQ on membrane lipid oxidation and structural organization.
Iodometric approaches were used to measure the effects of naphthalene and NQ on lipid hydroperoxide (LOOH) formation in model membranes composed of cholesterol (C) and dilinoleoylphosphatidylcholine (P). Membrane samples were prepared at a C/P mole ratio of 0.6 and subjected to autoxidation at 37°C for 48 hr in the absence or presence of either agent (0.1 to 5.0 µM). The effects of these agents on lipid peroxidation were also tested as a function of increasing C/P (0 to 1.0) or vitamin E concentration (0.1 to 5.0 µM, at 0.6 C/P). Small angle x-ray diffraction was used to measure the effects of naphthalene and NQ on membrane lipid organization before and after exposure to oxidative stress.
NQ increased LOOH formation by 250% (p<0.001) and 350% (p<0.001) at 1.0 and 5.0 µM, respectively, while naphthalene decreased LOOH formation by 25% (p<0.01) and 10% (n.s.). The pro-oxidant effect of NQ was inversely affected by membrane cholesterol content--as indicated by a progressive reduction in LOOH levels from 1274 ± 150 µM at 0 C/P to 744 ± 78 µM at 1.0 C/P--and was completely blocked by vitamin E. In contrast, the peroxidation effects of naphthalene were unaffected by either cholesterol or vitamin E treatment. X-ray diffraction results demonstrated that NQ increased membrane cholesterol domain formation by 185% following 48 hr exposure to oxidative stress; no changes in membrane lipid organization were observed with naphthalene.
These data suggest a novel mechanism for naphthalene-induced cataract, facilitated by the direct effects of NQ on lipid peroxidation and cholesterol domain formation.
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