Disease relevance of C06205

• The oxidation of naphthalene-1,2-dihydrodiol (ND) to o-naphthoquinone (NQ) in the lens is believed to be responsible for the formation of cataracts in naphthalene-fed rats [1].

High impact information on C06205

• Naphthalene-1,2-dihydrodiol at 50 microM also caused an increase in the specific activity of the DT-diaphorase, while at 10 microM no apparent change occurred in the cells [2].
• METHODS: Lenses from nontransgenic mice and from transgenic lines CAR222 and CAR648, with different levels of AR, were cultured in medium containing naphthalene-1,2-dihydrodiol (ND) with or without AR inhibitor AL1576 [3].
• Therefore, the metabolite formed from naphthalene-1,2-dihydrodiol by aldose reductase is 1,2-naphthoquinone [4].
• Studies using either recombinant rat lens (RLAR) or human muscle aldose reductase (HMAR) incubated in vitro with ND in the presence of NAD(P) verified that aldose reductase (EC 1.1.1.21) is the dihydrodiol dehydrogenase that catalyzes the oxidation of ND to NQ [1].
• With the membrane fraction of cultured bovine aortic endothelial cells, we found that 1,2-NQ was a potent inhibitor of eNOS with an IC(50) value of 1.4 muM, whereas trans-1,2-dihydroxy-1,2-dihydronaphthalene (1,2-DDN), a redox-negative naphthalene analog of 1,2-NQ, did not show such an inhibitory action [5].

Associations of C06205 with other chemical compounds

• CONCLUSIONS: The findings showed that the progression rate of ND-induced cataract correlated with the level of lens AR and ND, indicating that AR was the key enzyme for the metabolism of ND in the process of naphthalene cataract development [3].

Gene context of C06205

• Prevention of naphthalene-1,2-dihydrodiol-induced lens protein modifications by structurally diverse aldose reductase inhibitors [4].
• The stoichiometry of 1:1 between the consumption of ND and the formation of NADH for the formation of HNQ implies that rat lens aldose reductase catalyzes a 2e- oxidation of ND to yield the corresponding ketol, which is autoxidized to NQ [1].

Analytical, diagnostic and therapeutic context of C06205

• Comparison of the circular dichroism spectrum of the fungal trans-1,2-dihydroxy-1,2-dihydronaphthalene to that formed by mammalian enzyme systems indicated that the fungal dihydrodiol contained 76% (+)-(1S,2S)-dihydrodiol as the predominant enantiomer [6].

References