Quinone induced stimulation of hexose monophosphate shunt activity in the guinea pig lens: role of zeta-crystallin.
The response of the hexose monophosphate shunt (HMS) in organ-cultured guinea pig lens to 1,2-naphthoquinone and 5-hydroxy-1,4-naphthoquinone (juglone) has been investigated. Both these compounds, which are substrates of guinea pig lens zeta-crystallin (NADPH:quinone oxidoreductase), were found to cause increases in the rate of 14CO2 production from 1-14C-labelled glucose. Exposure of lenses to 15 microM 1,2-naphthoquinone or 20 microM juglone yielded 5.9- and 7-fold stimulation of HMS activity, respectively. Unlike hydrogen peroxide-induced stimulation of HMS activity, these effects were not abolished by preincubation with the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU). While hydrogen peroxide produced substantial decrements in lens glutathione (GSH) levels, incubation with quinones was not associated with a similar reduction in GSH concentration. Protein-bound NADPH content in quinone-exposed guinea pig lenses was decreased, with a concomitant increase in the amounts of free NADP+. This finding supported the involvement of zeta-crystallin bound NADPH in the in vivo enzymic reduction of quinones. Hydrogen peroxide, on the other hand, caused decreases in the level of free NADPH alone, serving to confirm our earlier inference that quinone stimulated increases in the guinea pig lens HMS could be mediated through zeta-crystallin NADPH:quinone oxidoreductase activity.
Rao
P
P
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD.
Zigler
J S
JS
D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D003459:Crystallins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D003459:Crystallins; D009285:Naphthoquinones; D009249:NADP; C040756:1,2-naphthoquinone; D006861:Hydrogen Peroxide; D002330:Carmustine; C005134:juglone