Effect of glutathione deprivation on lens metabolism.
1-Chloro-2,4-dinitrobenzene (CDNB) was used to conjugate glutathione (GSH) through the catalysis of lens glutathione S-transferase without the untoward oxidative damage to the lens mediated by GSH oxidants. A 2 hr treatment of the rat lens with 1 mM CDNB resulted in a nearly total depletion of lens GSH with neither formation of GSSG nor glutathione-protein mixed disulfides. Rubidium uptake was found to decrease linearly with the loss of GSH; nevertheless, ionic imbalance did not commence until more than 30% cation pump activity was lost. Glycolytic rate dropped following CDNB treatment, due probably to a decline in demand for ATP by the deactivated cation pump. 31P-NMR studies confirmed the irreversible loss of ATP. CDNB depletion of GSH resulted in a two-fold increase in 14CO2 production from [14C]-1-glucose. Whereas oxidative stress resulted in a six-fold increase in glucose utilization through the hexose monophosphate shunt (HMPS), CDNB-treated lenses showed no such stimulation. This indicated that the residual GSH following CDNB treatment was insufficient for the activation of the glutathione peroxidase-reductase-HMPS mechanism and raised the possibility that the increased glucose utilization might be due to mechanisms other than the HMPS. These results indicate an intimate correlation between the GSH content and major metabolic functions in the lens.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006019:Glycolysis; D066298:In Vitro Techniques; D007473:Ion Channels; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010427:Pentose Phosphate Pathway; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D004137:Dinitrochlorobenzene; D007473:Ion Channels; D000255:Adenosine Triphosphate; D012964:Sodium; D005978:Glutathione; D012413:Rubidium; D011188:Potassium