Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes

Shivali Gupta, Vandanajay Bhatia, Jian jun Wen, Yewen Wu, Ming He Huang, Nisha Jain Garg

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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-1β, TNF-α, and IFN-γ). 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 (ρ) 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.

Original languageEnglish (US)
Pages (from-to)1414-1421
Number of pages8
JournalFree Radical Biology and Medicine
Volume47
Issue number10
DOIs
StatePublished - Nov 15 2009

Keywords

  • Chagas disease
  • Inflammatory cytokines
  • Mitochondria
  • Primary cardiomyocytes
  • Reactive oxygen species
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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