HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

1,2-naphthoquinone stimulates lipid peroxidation and cholesterol domain formation in model membranes.

AbstractPURPOSE:
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.
AuthorsRobert F Jacob, Michael D Aleo, Yehudi Self-Medlin, Colleen M Doshna, R Preston Mason
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 54 Issue 12 Pg. 7189-97 (Nov 01 2013) ISSN: 1552-5783 [Electronic] United States
PMID24130176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lipid Peroxides
  • Membrane Lipids
  • Naphthalenes
  • Naphthoquinones
  • naphthalene
  • 1,2-naphthoquinone
  • Cholesterol
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: