In the previous granting period we have described perturbations in the biochemical pathways and function of human umbilical vein endothelial cells infected with Trypanosoma cruzi. In the present proposal we have extended these observations and have also included experiments to elucidate biochemical pathways that may be unique to this parasite and that any provide insight into infection-associated alterations of host cell signal transduction that ultimately lead to perturbation of microvascular perfusion. The experiments are divided into two sections. Infection-associated perturbations of endothelial cells will be investigated by determining the effect of the parasite on host cell gene expression as it relates to the compromise of microvascular perfusion. Secondly, we will continue to investigate how infection influences signal transduction systems of the host endothelial cell by examining single cell calcium mobilization. There is recent evidence that T. cruzi possess a complicated signal transduction system and we are therefore interested in how the signal transduction system of the parasite and host endothelial cell interact and perhaps modulate or modify the host-parasite relationship. Specifically, we plan to study how calcium and calmodulin may be involved in the parasite signal transduction system. In this regard, we will characterize the biochemical and functional properties of parasite calcium-dependent calmodulin binding proteins in all life cycle stages and in addition develop molecular probes in order to determine how calmodulin binding proteins function both in vitro and in intact cell systems. Finally, we will examine the metabolism of IP3 and phospholipase C in each life cycle stage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026368-05
Application #
3140159
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1988-04-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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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