Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 47, Issue 10, Pages 1414-1421Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.08.008
Keywords
Trypanosoma cruzi; Chagas disease; Primary cardiomyocytes; Mitochondria; Reactive oxygen species; Inflammatory cytokines
Funding
- National Institutes of Health/National institute of Allergy and Infectious Diseases [AI054578]
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In this study, we investigated the role of Trypanosoma cruzi invasion and inflammatory processes in reactive oxygen species (ROS) production in a mouse atrial cardiomyocyte line (HL-1) and primary adult rat ventricular cardiomyocytes. Cardiomyocytes were incubated with T. cruzi (Tc) trypomastigotes, Tc lysate (TcTL), or Tc secreted proteins (TcSP) for 0-72 h, and ROS were measured by amplex red assay. Cardiomyocytes infected by T cruzi (but not those incubated with TcTL or TcSP) exhibited a linear increase in ROS production for 2-48 h postinfection (max 18-fold increase), which was further enhanced by recombinant cytokines (IL-1 beta, TNF-alpha, and IFN-gamma). We observed no increase in NADPH oxidase, xanthine oxidase, or myeloperoxidase activity, and specific inhibitors of these enzymes did not block the increased rate of ROS production in infected cardiomyocytes. Instead, the mitochondrial membrane potential was perturbed and resulted in inefficient electron transport chain (ETC) activity and enhanced electron leakage and ROS formation in infected cardiomyocytes. HL-1 rho (rho) cardiomyocytes lacked a functional ETC and exhibited no increase in ROS formation in response to T cruzi. Together, these results demonstrate that invasion by T. cruzi and an inflammatory milieu affect mitochondrial integrity and contribute to electron transport chain inefficiency and ROS production in cardiomyocytes. (C) 2009 Elsevier Inc. All rights reserved.
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