Abstract | PURPOSE:
Naphthalene induces cataract formation through the accumulation of its reactive metabolite, 1,2-naphthoquinone (1,2-NQ), in the ocular lens. 1,2-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 1,2-NQ on membrane lipid oxidation and structural organization. METHODS: Iodometric approaches were used to measure the effects of naphthalene and 1,2-NQ on lipid hydroperoxide (LOOH) formation in model membranes composed of cholesterol and dilinoleoylphosphatidylcholine. Membrane samples were prepared at various cholesterol-to- phospholipid mole ratios and subjected to autoxidation at 37°C for 48 hours in the absence or presence of either agent alone (0.1-5.0 μM) or in combination with vitamin E. Small-angle x-ray diffraction was used to measure the effects of naphthalene and 1,2-NQ on membrane structure before and after exposure to oxidative stress. RESULTS: 1,2-NQ increased LOOH formation by 250% (P < 0.001) and 350% (P < 0.001) at 1.0 and 5.0 μM, respectively, whereas naphthalene decreased LOOH levels by 25% (P < 0.01) and 10% (NS). The pro-oxidant effect of 1,2-NQ was inversely affected by membrane cholesterol enrichment and completely blocked by vitamin E. 1,2-NQ also increased cholesterol domain formation by 360% in membranes exposed to oxidative stress; however, no significant changes in membrane lipid organization were observed with naphthalene under the same conditions. CONCLUSIONS: These data suggest a novel mechanism for naphthalene-induced cataract, facilitated by the direct effects of 1,2-NQ on lipid peroxidation and cholesterol domain formation.
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Authors | Robert F Jacob, Michael D Aleo, Yehudi Self-Medlin, Colleen M Doshna, R Preston Mason |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 54
Issue 12
Pg. 7189-97
(Nov 01 2013)
ISSN: 1552-5783 [Electronic] United States |
PMID | 24130176
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lipid Peroxides
- Membrane Lipids
- Naphthalenes
- Naphthoquinones
- naphthalene
- 1,2-naphthoquinone
- Cholesterol
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Topics |
- Analysis of Variance
- Cataract
(chemically induced)
- Cholesterol
(metabolism)
- Humans
- Lipid Peroxidation
(drug effects)
- Lipid Peroxides
(metabolism)
- Membrane Lipids
(analysis, chemistry, metabolism)
- Models, Biological
- Naphthalenes
(pharmacology)
- Naphthoquinones
(adverse effects, metabolism, pharmacology)
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