Glutathione protection in alveolar type II cells from fetal and neonatal rabbits.
Previous studies have demonstrated a correlation between intracellular glutathione (GSH) pools and sensitivity to oxidative injury. In the present study, we demonstrated that de novo GSH synthesis or GSH uptake could increase intracellular GSH by 7- and 19-fold, respectively, in type II cells from neonatal rabbits. This suggested that the rate of GSH uptake was against a concentration gradient and greater than the synthetic rate. This increased intracellular GSH was associated with protection from oxidant injury by paraquat or 80% O2. A relationship between GSH uptake and protection was further supported by blockage of both processes by gamma-L-glutamyl-L-glutamate, a GSH analogue. With a greater oxidative burden, both de novo synthesis and GSH uptake were required to maintain protection. Although the transport rate was only 6% of that for neonatal cells, cells from fetal animals transported GSH and were protected from oxidative injury. From these results we conclude there was a causal relationship between GSH transport and protection from oxidative injury in type II cells from neonatal and fetal animals.
Brown
L A
LA
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322.
Bai
C
C
Jones
D P
DP
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D011817:Rabbits
D000596:Amino Acids; D005978:Glutathione; D010269:Paraquat; D010100:Oxygen