Evidence that myocardial pertussis toxin substrates are uniquely altered in acute murine Chagas' disease in a manner unrelated to myocardial dysfunction.
In an effort to correlate biochemical characteristics of the beta-adrenergic receptor complex with myocardial function, mouse myocardial GTP-binding proteins, specifically substrates for pertussis toxin (PT), were analysed with regard to the influence of infection with Trypanosoma cruzi, the causative agent of Chagas' cardiomyopathy. Infection was found to decrease in a non-uniform manner the magnitude of ADP-ribosylation in the PT substrates. High detergent concentrations attenuated the infection-associated decrease in PT-dependent ADP-ribosylation. Infection also altered the kinetics of the PT-dependent ADP-ribosylation reaction from a time course wherein maximal PT-dependent ADP-ribosylation occurred after 12 h incubation in control animals to one in which maximal PT-dependent ADP-ribosylation occurred after 3 h incubation and thereafter declined. Immunochemical analysis of the PT-substrates revealed an infection-associated decrease in alpha i1, alpha o, an increase in alpha i2 and no change in alpha i3. Verapamil treatment, which prevents the clinical consequences of infection, did not influence any of the infection-associated changes in PT-dependent ADP-ribosylation of GTP-binding protein substrates or their immunochemical properties. Complementary studies using isolated rat neonatal cardiocytes infected with the parasite further substantiated the finding that the infection-associated decrease in PT-dependent ADP-ribosylation and the associated change in the kinetics of the reaction were properties uniquely associated with the presence of the parasite.
Huang
H
H
Department of Pathology and Neurosciences, Albert Einstein College of Medicine, Bronx, NY 10461.
Tanowitz
H B
HB
Oz
H S
HS
Wittner
M
M
Spray
D C
DC
Bilezikian
J P
JP
Morris
S A
SA
D000208:Acute Disease; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000378:metabolism; D014355:Chagas Disease / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins