TY - JOUR
T1 - Microarray analysis of the mammalian thromboxane receptor-Trypanosoma cruzi interaction
AU - Tanowitz, Herbert B.
AU - Mukhopadhyay, Aparna
AU - Ashton, Anthony W.
AU - Lisanti, Michael P.
AU - Machado, Fabiana S.
AU - Weiss, Louis M.
AU - Mukherjee, Shankar
N1 - Funding Information:
hour in dark. Finally the cells were washed in TBST for three This work was supported by Scientist Development Grant from times and observed under an Olympus 1X71 Microscope with the National affiliate of the American Heart Association (SDG 60x oil immersion objective. Immunofluorescence images were 0735252N to S.M.), NIH grant (AI-076248 to H.B.T.). We captured with a CoolSnap HQ cooled charge-coupled device acknowledge the assistance Vickie Braunstein for cell culture and camera (Roper Scientific, Trenton, NJ) and Cy2 excitation maintenance.
PY - 2011/4/1
Y1 - 2011/4/1
N2 - 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.
AB - 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.
KW - Chagel disease
KW - Microarray
KW - Suppressor of cytokine signaling
KW - Thromboxane signaling
KW - Trypanosoma cruzi
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U2 - 10.4161/cc.10.7.15207
DO - 10.4161/cc.10.7.15207
M3 - Article
C2 - 21364319
AN - SCOPUS:79953661972
SN - 1538-4101
VL - 10
SP - 1132
EP - 1143
JO - Cell Cycle
JF - Cell Cycle
IS - 7
ER -