title: 1,2-naphthoquinone stimulates lipid peroxidation and cholesterol domain formation in model membranes.
abstract: OBJECTIVE
  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.
authors.affiliation: Elucida Research LLC, Beverly, Massachusetts.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Jacob
authors.forename: Michael D
authors.initials: MD
authors.lastname: Aleo
authors.forename: Yehudi
authors.initials: Y
authors.lastname: Self-Medlin
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Doshna
authors.forename: R Preston
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000704:Analysis of Variance; D002386:Cataract / Q000139:chemically induced; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008563:Membrane Lipids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009281:Naphthalenes / Q000494:pharmacology; D009285:Naphthoquinones / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D008054:Lipid Peroxides; D008563:Membrane Lipids; D009281:Naphthalenes; D009285:Naphthoquinones; C031721:naphthalene; C040756:1,2-naphthoquinone; D002784:Cholesterol
keywords: 1,2-naphthoquinone; cataractogenesis; cholesterol domains; lipid peroxidation; naphthalene