Metabolic changes in alveolar type II cells after exposure to hydrogen peroxide.
Since oxygen metabolites may play an important role in pulmonary oxidant injury, the effects of hydrogen peroxide (H2O2) on energy metabolism in alveolar type II cells isolated from rats were studied. The major effect of H2O2 is a rapid and dramatic reduction in the steady-state level of cellular ATP; e.g., ATP levels are reduced by 77 +/- 3% after only 5 min of exposure to H2O2 (0.5 mM). Cellular oxygen consumption is affected in a similar manner, suggesting that ATP synthesis is impaired. Experiments with isolated lung mitochondria demonstrate that exposure to 0.5 mM H2O2 for 5 min inhibits the rate of mitochondrial ATP synthesis by 51 +/- 3%. The site of mitochondrial ATP synthesis inhibition by H2O2 appears to be the adenosinetriphosphatase-synthase enzyme complex which phosphorylates ADP to ATP. Mitochondrial electron transport is unaffected. The association of 3-O-methylglucose with type II cells and glycolytic metabolism, measured as lactate production, are reduced by 25-35% by H2O2. The data also show that the cells are capable of recovery following exposure to H2O2, at least at lower exposure levels. These results indicate that exposure of type II cells to H2O2 alters the energy state of the cells by decreasing ATP synthesis. In turn, other important cellular functions may be impaired.
LaCagnin
L B
LB
Division of Respiratory Disease Studies, Appalachian Laboratory for Occupational Safety and Health, Morgantown 26505.
Bowman
L
L
Ma
J Y
JY
Miles
P R
PR
D019325:3-O-Methylglucose; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000494:pharmacology
D007773:Lactates; D008757:Methylglucosides; D019325:3-O-Methylglucose; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D005947:Glucose; D012966:Sodium Cyanide