In previous studies from out laboratory we have detailed the effect of Trypanosoma cruzi infection on the generation of intracellular second messengers such as cAMP and calcium. The mechanism of these effects seems to be at the level of the guanine nucleotide binding proteins. We have also described the effect of verapamil on the course of murine Chagas' disease, again implicating calcium as an important factor in the pathogenesis of the cardiomyopathy that attends this infection. We and others have made the observation that the extent of parasitism is unrelated to the functional impairment. Consequently, this has led us to an examination of the intracellular communication between infected and uninfected cells. In an effort to understand this relationship we will study coordinated communication between infected and uninfected myoblasts and between infected and uninfected cardiocytes via gap junctions. We will study whether T.cruzi infection results in altered expression of gap junctions. Toward this end we will compare gap junctions mRNA levels and immunolocalized gap junctions in infected and uninfected myoblasts and cardiocytes. We will also study the influence of infection on receptor-dependent and independent mobilization of intracellular calcium in single cells. The role of phospholipdid metabolism in this process will also be investigated. Finally, since we have already shown in a murine model that verapamil, a calcium channel blocker ameliorates the consequences of this infection on the heart we will determine the mode of action of this agent and other related compounds on intracellular calcium metabolism in infected myoblasts and cardiocytes. Alterations in intracellular calcium metabolism and gap junction expression may explain, in part, the contractility and electrical conduction abnormalities that attends Chagas' disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012770-13
Application #
3125290
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1978-07-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
13
Fiscal Year
1990
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
Souza, Andrea P de; Jelicks, Linda A; Tanowitz, Herbert B et al. (2010) The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice. Mem Inst Oswaldo Cruz 105:746-51
Adesse, Daniel; Garzoni, Luciana R; Huang, Huan et al. (2008) Trypanosoma cruzi induces changes in cardiac connexin43 expression. Microbes Infect 10:21-8
Petkova, S B; Huang, H; Factor, S M et al. (2001) The role of endothelin in the pathogenesis of Chagas' disease. Int J Parasitol 31:499-511
Petkova, S B; Tanowitz, H B; Magazine, H I et al. (2000) Myocardial expression of endothelin-1 in murine Trypanosoma cruzi infection. Cardiovasc Pathol 9:257-65