Effect of glutathione depletion on cation transport and metabolism in the rabbit lens.
The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70-90% led to a decrease in uptake and increase in efflux of 86Rb. ATP levels and Na+/K+-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na+/K+-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H2O2 showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na+/K+ pump, thus leading to ionic changes and cataract development.
Reddy
V N
VN
Eye Research Institute, Oakland University, Rochester, Mich.
Garadi
R
R
Chakrapani
B
B
Giblin
F J
FJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D002412:Cations / Q000378:metabolism*; D046508:Culture Techniques; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology / Q000378:metabolism*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002412:Cations; D004137:Dinitrochlorobenzene; D000255:Adenosine Triphosphate; D012964:Sodium; D006861:Hydrogen Peroxide; D005978:Glutathione; D012413:Rubidium; D011188:Potassium