Pertussis toxin alters the concentration and turnover of manganese superoxide dismutase in rat lung.
Treatment of rats with pertussis toxin (PTX) decreases the activity of manganese superoxide dismutase (Mn-SOD) in the lung and results in oxygen toxicity in air (L. B. Clerch, G. Neithardt, U. Spencer, J. A. Melendez, G. D. Massaro, and D. Massaro. J. Clin. Invest. 93: 2482-2489, 1994). To examine aspects of the mechanism of the PTX-induced fall in Mn-SOD activity, we injected rats with PTX (50 micrograms/kg), killed the rats 72 h later, and measured the activity, concentration, specific activity, and turnover of Mn-SOD in the lung. Treatment with PTX caused an approximately 50% fall in Mn-SOD activity and Mn-SOD concentration but no change in Mn-SOD specific activity. PTX also caused an increase in Mn-SOD mRNA concentration, a fall in Mn-SOD synthesis, and an increase in the half-life of Mn-SOD and general proteins. We conclude the PTX-induced low concentration of Mn-SOD is due to a decrease of translational efficiency. We suggest that, under normoxic conditions, signal transduction via heterotrimeric guanine nucleotide binding proteins regulates the expression of Mn-SOD at the level of translation and Mn-SOD degradation.
Berkovich
A
A
Department of Pediatrics, Georgetown University School of Medicine, Washington, District of Columbia 20007-2197, USA.
Massaro
D
D
Clerch
L B
LB
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D008168:Lung / Q000201:enzymology*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D013482:Superoxide Dismutase; D037342:Pertussis Toxin