Evidence that Myocardial Pertussis Toxin Substrates are Uniquely Altered in Acute Murine Chagas' Disease in a Manner Unrelated to Myocardial Dysfunction

Huan Huang, Herbert B. Tanowitz, Helieh S. Oz, Murray Wittner, David C. Spray, John P. Bilezikian, Stephen A. Morris

Research output: Contribution to journalArticle

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Abstract

In an effort to correlate biochemical characteristics of the β-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 αi1, αo, an increase in αi2 and no change in αi3. 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.

Original languageEnglish (US)
Pages (from-to)1293-1304
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume25
Issue number11
DOIs
StatePublished - Nov 1993

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Chagas Disease
Pertussis Toxin
Adenosine Diphosphate
Infection
GTP-Binding Proteins
Parasites
Chagas Cardiomyopathy
Trypanosoma cruzi
Verapamil
Detergents
Adrenergic Receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Cite this

Evidence that Myocardial Pertussis Toxin Substrates are Uniquely Altered in Acute Murine Chagas' Disease in a Manner Unrelated to Myocardial Dysfunction. / Huang, Huan; Tanowitz, Herbert B.; Oz, Helieh S.; Wittner, Murray; Spray, David C.; Bilezikian, John P.; Morris, Stephen A.

In: Journal of Molecular and Cellular Cardiology, Vol. 25, No. 11, 11.1993, p. 1293-1304.

Research output: Contribution to journalArticle

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abstract = "In an effort to correlate biochemical characteristics of the β-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 αi1, αo, an increase in αi2 and no change in αi3. 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.",
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