Abstract

Previous work in our laboratory has demonstrated that the coronary microcirculation is markedly impaired during the course of Trypanosoma cruzi infection. These observations have led us to consider that these early alterations lead to the focal pathology that attends chronic Chagasic cardiomypathy. Based on preliminary data concerning the interaction of T. cruzi infection- associated alterations in the mobilization of intracellular cAMP and Ca++ profoundly alter cellular function. This proposal examines the influence of T. cruzi infection on receptor complexes and related organelles involved in the generation and mobilization of cAMP and Ca++, respectively. With regard to the former, we shall examine the influence of parasite infection on the biochemical basis by which components of the adenylate cyclase complex i.e. receptors (R), guanine nucleotide binding proteins (Ns and Ni) and catalytic unit, interact in the generation of cAMP. In like manner, we shall investigate the influence of T. cruzi infection on Ca++ mobilization in endothelial host cells. Infection associated changes in the receptor populations involved in the mobilization of intracellular Ca++, and the generation of inositol phosphates will be examined. The possibility that infection alters storage of intracellular calcium will be explored. These studies will help characterize the influence of T. cruzi infection on biochemical systems known to regulate cell function, and may suggest potential therapeutic strategies for the treatment of this as yet incurable disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI026368-01
Application #
3140153
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Tanowitz, H B; Kaul, D K; Chen, B et al. (1996) Compromised microcirculation in acute murine Trypanosoma cruzi infection. J Parasitol 82:124-30
Wittner, M; Christ, G J; Huang, H et al. (1995) Trypanosoma cruzi induces endothelin release from endothelial cells. J Infect Dis 171:493-7
Oz, H S; Huang, H; Wittner, M et al. (1994) Evidence for guanosine triphosphate--binding proteins in Trypanosoma cruzi. Am J Trop Med Hyg 50:620-31
Factor, S M; Tanowitz, H; Wittner, M et al. (1993) Interstitial connective tissue matrix alterations in acute murine Chagas' disease. Clin Immunol Immunopathol 68:147-52
Tanowitz, H B; Gumprecht, J P; Spurr, D et al. (1992) Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi. J Infect Dis 166:598-603
Orr, G A; Tanowitz, H B; Wittner, M (1992) Trypanosoma cruzi: stage expression of calmodulin-binding proteins. Exp Parasitol 74:127-33
Oz, H S; Wittner, M; Tanowitz, H B et al. (1992) Trypanosoma cruzi: mechanisms of intracellular calcium homeostasis. Exp Parasitol 74:390-9
de Carvalho, A C; Tanowitz, H B; Wittner, M et al. (1992) Gap junction distribution is altered between cardiac myocytes infected with Trypanosoma cruzi. Circ Res 70:733-42
Morris, S A; Barr, S; Weiss, L et al. (1991) Myocardial beta-adrenergic adenylate cyclase complex in a canine model of chagasic cardiomyopathy. Circ Res 69:185-95
Simon, D; Weiss, L M; Tanowitz, H B et al. (1991) Light microscopic diagnosis of human microsporidiosis and variable response to octreotide. Gastroenterology 100:271-3

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