Ascorbate deficiency and oxidative stress in the alveolar type II cell.
The objective of this study was to determine the impact of limited ascorbate (Asc) availability on type II cell sensitivity to oxidant stress. Guinea pigs were fed diets with or without Asc for 18 days, and type II cells were isolated. Although lung Asc was decreased by 90% in deficient animals (scorbutic), type II cell Asc was decreased by 50%. Upon treatment with 250 microM H2O2, the necrotic injury was twofold greater in scorbutic cells compared with control cells. With 100 microM H2O2 treatment, apoptotic injury was twofold greater in scorbutic cells compared with control cells. Although there was less necrotic injury in cells exposed to 95% O2, the scorbutic cells were more sensitive than control cells. Asc pretreatment protected against necrosis and apoptosis. The Asc analog isoascorbate provided partial protection and suggested that part of the protection was not chemical detoxification but was Asc specific. We conclude that limited Asc availability resulted in a functional type II cell but a cell more sensitive to oxidant-induced injury.
Brown
L A
LA
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Harris
F L
FL
Jones
D P
DP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D006861:Hydrogen Peroxide; D001205:Ascorbic Acid