Pertussis toxin treatment alters manganese superoxide dismutase activity in lung. Evidence for lung oxygen toxicity in air-breathing rats.
Exposure of rats to hyperoxia or to treatment with endotoxin, increases lung manganese superoxide dismutase (MnSOD) gene expression. However, the paths by which these environmental signals are transduced into enhanced MnSOD gene expression are unknown. We now provide evidence that heterotrimeric G proteins are involved in the hyperoxia-induced increase in lung MnSOD gene expression but that pertussis toxin-sensitive G proteins are not involved in the endotoxin-induced elevation of lung MnSOD gene expression. We also show that treating rats with pertussis toxin decreased lung MnSOD activity approximately 50%. This decline in MnSOD activity occurred without a change in the lung activity of copper-zinc SOD, catalase, or glutathione peroxidase. In air-breathing rats, the pertussis toxin-induced decrease in MnSOD activity was associated with the development of lung edema, pleural effusion with a high concentration of protein, and biochemical evidence of lung oxygen toxicity. Compared to air-breathing rats, maintenance of pertussis toxin-treated rats under hypoxic or hyperoxic conditions respectively decreased or increased intrathoracic fluid. Endotoxin treatment elevated lung MnSOD activity and protected pertussis toxin-treated rats from an increase in intrathoracic fluid.
Clerch
L B
LB
Lung Biology Laboratory, Georgetown University School of Medicine, Washington, DC 20007.
Neithardt
G
G
Spencer
U
U
Melendez
J A
JA
Massaro
G D
GD
Massaro
D
D
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008345:Manganese; D010100:Oxygen / Q000633:toxicity*; D037342:Pertussis Toxin; D010996:Pleural Effusion / Q000209:etiology; D011654:Pulmonary Edema / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004731:Endotoxins; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D008345:Manganese; D013482:Superoxide Dismutase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D010100:Oxygen