Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase.
The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, causes severe morbidity and mortality in afflicted individuals. About 30% of T. cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or neurological disorders. Megacolon, one of the major patholo...
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ftdoajarticles:oai:doaj.org/article:b6ef11e7f31d42408564fe87c84ee677 2023-05-15T15:16:41+02:00 Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. Shankar Suman Girish Rachakonda Sammed N Mandape Shruti S Sakhare Fernando Villalta Siddharth Pratap Maria F Lima Pius N Nde 2018-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006792 https://doaj.org/article/b6ef11e7f31d42408564fe87c84ee677 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0006792 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006792 https://doaj.org/article/b6ef11e7f31d42408564fe87c84ee677 PLoS Neglected Tropical Diseases, Vol 12, Iss 9, p e0006792 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006792 2022-12-31T13:53:10Z The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, causes severe morbidity and mortality in afflicted individuals. About 30% of T. cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or neurological disorders. Megacolon, one of the major pathologies of Chagas disease, is accompanied by gastrointestinal motility disorders. The molecular mechanism of T. cruzi-mediated megacolon in Chagas disease is currently unknown. To decipher the molecular mechanism of T. cruzi-induced alteration in the colon during the early infection phase, we exposed primary human colonic epithelial cells (HCoEpiC) to invasive T. cruzi trypomastigotes at multiple time points to determine changes in the phosphoprotein networks in the cells following infection using proteome profiler Human phospho-kinase arrays. We found significant changes in the phosphorylation pattern that can mediate cellular deregulations in colonic epithelial cells after infection. We detected a significant increase in the levels of phosphorylated heat shock protein (p-HSP) 27 and transcription factors that regulate various cellular functions, including c-Jun and CREB. Our study confirmed significant upregulation of phospho (p-) Akt S473, p-JNK, which may directly or indirectly modulate CREB and c-Jun phosphorylation, respectively. We also observed increased levels of phosphorylated CREB and c-Jun in the nucleus. Furthermore, we found that p-c-Jun and p-CREB co-localized in the nucleus at 180 minutes post infection, with a maximum Pearson correlation coefficient of 0.76±0.02. Increased p-c-Jun and p-CREB have been linked to inflammatory and profibrotic responses. T. cruzi infection of HCoEpiC induces an increased expression of thrombospondin-1 (TSP-1), which is fibrogenic at elevated levels. We also found that T. cruzi infection modulates the expression of NF-kB and JAK2-STAT1 signaling molecules which can increase pro-inflammatory flux. Bioinformatics analysis of the phosphoprotein networks derived using the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 9 e0006792 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Shankar Suman Girish Rachakonda Sammed N Mandape Shruti S Sakhare Fernando Villalta Siddharth Pratap Maria F Lima Pius N Nde Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, causes severe morbidity and mortality in afflicted individuals. About 30% of T. cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or neurological disorders. Megacolon, one of the major pathologies of Chagas disease, is accompanied by gastrointestinal motility disorders. The molecular mechanism of T. cruzi-mediated megacolon in Chagas disease is currently unknown. To decipher the molecular mechanism of T. cruzi-induced alteration in the colon during the early infection phase, we exposed primary human colonic epithelial cells (HCoEpiC) to invasive T. cruzi trypomastigotes at multiple time points to determine changes in the phosphoprotein networks in the cells following infection using proteome profiler Human phospho-kinase arrays. We found significant changes in the phosphorylation pattern that can mediate cellular deregulations in colonic epithelial cells after infection. We detected a significant increase in the levels of phosphorylated heat shock protein (p-HSP) 27 and transcription factors that regulate various cellular functions, including c-Jun and CREB. Our study confirmed significant upregulation of phospho (p-) Akt S473, p-JNK, which may directly or indirectly modulate CREB and c-Jun phosphorylation, respectively. We also observed increased levels of phosphorylated CREB and c-Jun in the nucleus. Furthermore, we found that p-c-Jun and p-CREB co-localized in the nucleus at 180 minutes post infection, with a maximum Pearson correlation coefficient of 0.76±0.02. Increased p-c-Jun and p-CREB have been linked to inflammatory and profibrotic responses. T. cruzi infection of HCoEpiC induces an increased expression of thrombospondin-1 (TSP-1), which is fibrogenic at elevated levels. We also found that T. cruzi infection modulates the expression of NF-kB and JAK2-STAT1 signaling molecules which can increase pro-inflammatory flux. Bioinformatics analysis of the phosphoprotein networks derived using the ... |
format |
Article in Journal/Newspaper |
author |
Shankar Suman Girish Rachakonda Sammed N Mandape Shruti S Sakhare Fernando Villalta Siddharth Pratap Maria F Lima Pius N Nde |
author_facet |
Shankar Suman Girish Rachakonda Sammed N Mandape Shruti S Sakhare Fernando Villalta Siddharth Pratap Maria F Lima Pius N Nde |
author_sort |
Shankar Suman |
title |
Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
title_short |
Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
title_full |
Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
title_fullStr |
Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
title_full_unstemmed |
Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase. |
title_sort |
phospho-proteomic analysis of primary human colon epithelial cells during the early trypanosoma cruzi infection phase. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006792 https://doaj.org/article/b6ef11e7f31d42408564fe87c84ee677 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 9, p e0006792 (2018) |
op_relation |
https://doi.org/10.1371/journal.pntd.0006792 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006792 https://doaj.org/article/b6ef11e7f31d42408564fe87c84ee677 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006792 |
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PLOS Neglected Tropical Diseases |
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12 |
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9 |
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e0006792 |
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1766346973420453888 |