Homeostasis of the small airway epithelial (SAE) cell monolayer likely is pivotal to maintain defenses against lung insults. We examined the effects of antioxidant vitamins (vitamins C and E) and mononucleotides (AMP and UMP) on homeostasis of human SAE cells (Clonetics); nucleotides may protect against oxidant DNA damage or stress-induced apoptosis. Subconfluent and near-confluent SAE cells were cultured for 2 days in normoxia or hyperoxia (95% O2). Total cell number and viability, thymidme incorporation, LDH release, and apoptotic changes were measured. In normoxic subconfluence, there was minimal apoptosis but significant thymidine incorporation. Normoxic near-confluent cells had more significant apoptosis and loner thymidine incorporation than subconfluent cells along with more detached non-viable cells. Hyperoxia suppressed thymidine incorporation and augmented apoptosis in both sub- and near-confluent cells, but the effects were greater in subconfluence. Necrosis, as indicated by LDH release, was minimal m all conditions. Vitamin E (10-7 mol/L) prevented the hyperoxic decline of thymidine incorporation in subconfluence and protected against hyperoxia-induced apoptosis in both subconfluence and near-confluence (p<0.02). Vitamin C (10-7 mol/L) prevented apoptosis in hyperoxia only in near-confluence (p<0.05). UMP and AMP (10-100 μmol/L) prevented hyperoxia-induced apoptosis in near-confluence (p<0.05) but not in subconfluence. Confluence determines the homeostasis of SAE cells and the effects of hyperoxia and protection by vitamins and nucleotides.
|Original language||English (US)|
|State||Published - Dec 1 1997|