Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes.
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-1beta, 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.
Gupta
Shivali
S
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Bhatia
Vandanajay
V
Wen
Jian-jun
JJ
Wu
Yewen
Y
Huang
Ming-He
MH
Garg
Nisha Jain
NJ
D000818:Animals; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000737:chemistry; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000276:immunology*; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification*
D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D014344:Trypanocidal Agents
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