Microarray analysis of the mammalian thromboxane receptor-Trypanosoma cruzi interaction

Herbert B. Tanowitz, Aparna Mukhopadhyay, Anthony W. Ashton, Michael P. Lisanti, Fabiana S. Machado, Louis M. Weiss, Shankar Mukherjee

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Trypanosoma cruzi, the etiological agent of Chagas disease, causes vasculopathy and cardiomyopathy in humans and is associated with elevated levels of several vasoactive molecules such as nitric oxide, endothelin-1 and thromboxane A2 (TXA2). Parasite derived TXA2 modulates vasculopathy and other pathophysiological features of chagasic cardiomyopathy. Previously, we demonstrated that in response to infection with T. cruzi, TXA2 receptor (TP ) null mice displayed increased parasitemia; mortality and cardiac pathology compared with wild type (WT) and TXA2 synthase null mice. In order to further study the role of TXA2-TP signaling in the development of Chagas disease, GeneChip microarrays were used to detect transcriptome changes in rat fat pad endothelial cells (RFP-ECs) which is incapable of TXA2 signaling (TP null) to that of control (wild type) and RFP-EC with reconstituted TP expression. Genes that were significantly regulated due to infection were identified using a time course of 2, 18 and 48 hrs post infection. We identified several key genes such as suppressor of cytokine signaling (SOCS-5), several cytokines (CSF-1, CXCF ligands) and MAP kinases (MAPK-1, Janus kinase) that were upregulated in the absence of TP signaling. These data underscore the importance of the interaction of the parasite with mammalian TP and may explain the increased mortality and cardiovascular pathology observed in infected TP null mice.

Original languageEnglish (US)
Pages (from-to)1132-1143
Number of pages12
JournalCell Cycle
Volume10
Issue number7
DOIs
StatePublished - Apr 1 2011

Keywords

  • Chagel disease
  • Microarray
  • Suppressor of cytokine signaling
  • Thromboxane signaling
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Tanowitz, H. B., Mukhopadhyay, A., Ashton, A. W., Lisanti, M. P., Machado, F. S., Weiss, L. M., & Mukherjee, S. (2011). Microarray analysis of the mammalian thromboxane receptor-Trypanosoma cruzi interaction. Cell Cycle, 10(7), 1132-1143. https://doi.org/10.4161/cc.10.7.15207