Regulation of the synthesis of superoxide dismutases in rat lungs during oxidant and hyperthermic stresses.
Heat shock proteins are induced at normal temperatures by oxidants and during reoxygenation following hypoxia. We now report cyanide-resistant O2 consumption increased 30-50% in rat lungs exposed to heat shock or reoxygenation following hypoxia. The synthesis of Cu,Zn superoxide dismutase, but not Mn superoxide dismutase, was increased in rat lung slices by in vivo hyperthermia (39 degrees C), by in vitro heat shock (41 degrees C), and during incubation of lung slices with the Cu chelator diethyldithiocarbamate, which decreased the activity of Cu,Zn superoxide dismutase. The heat shock-induced increase in Cu,Zn superoxide dismutase developed 2 h later than the induction of heat shock proteins and was not blocked by actinomycin D. The rates of synthesis of both superoxide dismutases were decreased 50% by hypoxia and failed to increase during reoxygenation. During hypoxia the activity of Cu,Zn superoxide dismutase decreased about 50%, but the activity of Mn superoxide dismutase remained unchanged. We conclude that hyperthermia increases the synthesis of Cu,Zn superoxide dismutase, the synthesis of Cu,Zn superoxide dismutase and Mn superoxide dismutase are not coordinately regulated by hyperthermia or by the oxidant stress produced by lowering the activity of Cu,Zn superoxide dismutase, and the synthesis of heat shock proteins and Cu,Zn superoxide dismutase are regulated at different levels of gene expression.
Hass
M A
MA
Calvin and Flavia Oak Asthma Research and Treatment Facility, University of Miami School of Medicine, Florida 33101.
Massaro
D
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D000596:Amino Acids / Q000032:analysis; D000818:Animals; D003300:Copper / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005334:Fever / Q000201:enzymology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D000860:Hypoxia / Q000201:enzymology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000378:metabolism; D008970:Molecular Weight; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D015032:Zinc / Q000378:metabolism
D000596:Amino Acids; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D003609:Dactinomycin; D008345:Manganese; D003300:Copper; D004050:Ditiocarb; D013482:Superoxide Dismutase; D015032:Zinc