Trypanosoma cruzi infection (Chagas' disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium

H. Huang, S. B. Petkova, R. G. Pestell, B. Bouzahzah, J. Chan, H. Magazine, L. M. Weiss, G. J. Christ, M. P. Lisanti, S. A. Douglas, V. Shtutin, S. K. Halonen, M. Wittner, H. B. Tanowitz

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Chagas' disease, caused by the parasite Trypanosoma cruzi, is an important cause of heart disease. Previous studies from this laboratory revealed that microvascular spasm and myocardial ischemia were observed in infected mice. Infection of endothelial cells with this parasite increased the synthesis of biologically active endothelin-1 (ET-1). Therefore, in the myocardium of T. cruzi-infected mice, we examined ET-1 expression and the p42/44-mitogen activated protein kinase (MAPK)-AP-1 pathway that regulates the expression of ET-1. There was parasitism and myonecrosis in the myocardium of infected C57BL/6 mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed elevated mRNA expression of transcription factor AP-1 (c-jun and c-fos) and increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assay (EMSA). Western blot analysis demonstrated an increase in the phosphorylated forms of extracellular signal-regulated kinase (ERK1/2). ET-1 mRNA was upregulated in the myocardium of infected mice. Immunohistochemical and immunoelectron microscopy using anti-ET-1 antibody detected increased expression in cardiac myocytes and endothelium of these mice. These data suggest that ET-1 contributes to chagasic cardiomyopathy and that the mechanism of the increased expression of ET-1 is a result of the activation of the MAPK pathway by T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)S148-S150
JournalJournal of Cardiovascular Pharmacology
Volume36
Issue number5 SUPPL. 1
DOIs
StatePublished - 2000

Keywords

  • Activator protein-1 (AP-1)
  • Chagas' disease
  • Endothelin (ET)
  • Extracellular signal-regulated kinase (ERK)
  • Mitogen-activated protein kinase (MAPK)
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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