Selenite-lnduced Damage to Lens Membranes

Abstract

The present study focuses on three aspects of membrane damage to explain selenite-induced loss of ion homeostasis: membrane transport processes, i.e. cation pump; biosynthesis of membrane proteins and membrane permeability. Cation pump activity, assessed by both 86Rb uptake and Na K-ATPase activity in the epithelium, was observed to decline gradually after exposure to selenite and subsequent culture for 2 days in a selenite-free medium. In fact, the major loss of transport and ATPase activity occurred during culture of lenses after transfer from selenite to a selenite-free medium. The delay between selenite presentation to the lens and final inhibition of the cation pump (47%) corresponds to the delay in the observed loss of Na-K-ATPase activity (50%). Initial loss of cation transport and Na-K-ATPase activity may be due to the oxidative capacity of selenite. Oxidation, however, might not explain the delayed, progressive loss of transport activity after selenite removal. A plausible cause for this sustained loss might be a depleted supply of Na-K-ATPase due to impaired biosynthesis. Evidence for such a possibility comes from the observation that the rate of synthesis of total membrane protein is impaired by 44% in selenite-treated lenses. Membrane permeability to Na + was not affected at the end of day 1, a conclusion based on the following observation: ouabain-treated lenses exposed to selenite did not gain any more Na + than did ouabain-treated lenses. With the pump blocked by ouabain in both groups of lenses, the passive influx of Na + was unchanged by selenite, indicating little damage to membrane permeability. Further changes in permeability during extended culture, possibly due to hydration and osmotic stress, may contribute to irreversible ionic imbalances observed after removal of selenite. In conclusion, selenite damage to lens membranes was initially limited to the cation transport system, with impaired protein synthesis possibly contributing to delayed and sustained loss of transport activity.