Endotoxin induces glutathione reductase activity in lungs of mice.
Glutathione reductase catalyzes the NADPH-dependent conversion of glutathione disulfide to glutathione and helps protect the lung from injury by reactive oxygen. In animals allowed to breathe nearly 100% oxygen, the activities of other antioxidants in the lung can be induced by treatment with endotoxin, and this induction is associated with increased tolerance to hyperoxia. The purpose of this study was to see whether glutathione reductase activity in the lungs of mice increased with endotoxin treatment alone. We studied 60 FVB mice (20 males and 40 females). Half received endotoxin (500 micrograms/kg) intraperitoneally at time 0 and 24 h, and the controls received an equal volume of saline. At 48 h we killed the mice and removed their lungs. Treatment of mice with endotoxin increased glutathione reductase activity in the lung 55% (0.035 +/- 0.005 to 0.054 +/- 0.010 mumol NADPH reduced/min/mg protein; mean +/- SD; endotoxin different from control, p < 0.001). The increase in activity was the same for male and female mice. We measured the specific protein for glutathione reductase by Western analysis and mRNA for glutathione reductase using a slot-blot analysis and found that both increased roughly 2-fold with endotoxin treatment. This suggests that endotoxin treatment resulted in either increased rate of transcription of glutathione reductase mRNA or increased mRNA stability. We conclude that endotoxin treatment increases glutathione reductase activity in the lung and that this increase in activity may play a role in subsequent protection from hyperoxia.
Hamburg
D C
DC
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Tonoki
H
H
Welty
S E
SE
Geske
R S
RS
Montgomery
C A
CA
Hansen
T N
TN
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005980:Glutathione Reductase / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D055370:Lung Injury; D008297:Male; D051379:Mice; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity
D000975:Antioxidants; D004731:Endotoxins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005980:Glutathione Reductase; D010100:Oxygen