Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease.
Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy contr...
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ftdoajarticles:oai:doaj.org/article:2c150de3294b493f9cceec800b7074a9 2023-05-15T15:15:05+02:00 Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. Nisha Jain Garg Kizhake V Soman Maria P Zago Sue-Jie Koo Heidi Spratt Susan Stafford Zinzi N Blell Shivali Gupta Julio Nuñez Burgos Natalia Barrientos Allan R Brasier John E Wiktorowicz 2016-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004490 https://doaj.org/article/2c150de3294b493f9cceec800b7074a9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4769231?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004490 https://doaj.org/article/2c150de3294b493f9cceec800b7074a9 PLoS Neglected Tropical Diseases, Vol 10, Iss 2, p e0004490 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004490 2022-12-31T14:07:43Z Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction. Protein samples were labeled with BODIPY FL-maleimide (dynamic range: > 4 orders of magnitude, detection limit: 5 f-mol) and resolved by two-dimensional gel electrophoresis (2D-GE). After normalizing the gel images, protein spots that exhibited differential abundance in any of the two groups were analyzed by mass spectrometry, and searched against UniProt human database for protein identification. We found 213 and 199 protein spots (fold change: |≥ 1.5|, p< 0.05) were differentially abundant in C/A and C/S individuals, respectively, with respect to N/H controls. Ingenuity Pathway Analysis (IPA) of PBMCs proteome dataset identified an increase in disorganization of cytoskeletal assembly and recruitment/activation and migration of immune cells in all chagasic subjects, though the invasion capacity of cells was decreased in C/S individuals. IPA predicted with high probability a decline in cell survival and free radical scavenging capacity in C/S (but not C/A) subjects. The MYC/SP1 transcription factors that regulate hypoxia and oxidative/inflammatory stress were predicted to be key targets in the context of control of Chagas disease severity. Further, MARS-modeling identified a panel of proteins that had >93% prediction success in classifying infected individuals with no disease and those with cardiac involvement and LV dysfunction. In conclusion, we have identified molecular pathways and a panel of proteins that could aid in detecting seropositive individuals at risk of developing ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 2 e0004490 |
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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 Nisha Jain Garg Kizhake V Soman Maria P Zago Sue-Jie Koo Heidi Spratt Susan Stafford Zinzi N Blell Shivali Gupta Julio Nuñez Burgos Natalia Barrientos Allan R Brasier John E Wiktorowicz Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction. Protein samples were labeled with BODIPY FL-maleimide (dynamic range: > 4 orders of magnitude, detection limit: 5 f-mol) and resolved by two-dimensional gel electrophoresis (2D-GE). After normalizing the gel images, protein spots that exhibited differential abundance in any of the two groups were analyzed by mass spectrometry, and searched against UniProt human database for protein identification. We found 213 and 199 protein spots (fold change: |≥ 1.5|, p< 0.05) were differentially abundant in C/A and C/S individuals, respectively, with respect to N/H controls. Ingenuity Pathway Analysis (IPA) of PBMCs proteome dataset identified an increase in disorganization of cytoskeletal assembly and recruitment/activation and migration of immune cells in all chagasic subjects, though the invasion capacity of cells was decreased in C/S individuals. IPA predicted with high probability a decline in cell survival and free radical scavenging capacity in C/S (but not C/A) subjects. The MYC/SP1 transcription factors that regulate hypoxia and oxidative/inflammatory stress were predicted to be key targets in the context of control of Chagas disease severity. Further, MARS-modeling identified a panel of proteins that had >93% prediction success in classifying infected individuals with no disease and those with cardiac involvement and LV dysfunction. In conclusion, we have identified molecular pathways and a panel of proteins that could aid in detecting seropositive individuals at risk of developing ... |
format |
Article in Journal/Newspaper |
author |
Nisha Jain Garg Kizhake V Soman Maria P Zago Sue-Jie Koo Heidi Spratt Susan Stafford Zinzi N Blell Shivali Gupta Julio Nuñez Burgos Natalia Barrientos Allan R Brasier John E Wiktorowicz |
author_facet |
Nisha Jain Garg Kizhake V Soman Maria P Zago Sue-Jie Koo Heidi Spratt Susan Stafford Zinzi N Blell Shivali Gupta Julio Nuñez Burgos Natalia Barrientos Allan R Brasier John E Wiktorowicz |
author_sort |
Nisha Jain Garg |
title |
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
title_short |
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
title_full |
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
title_fullStr |
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
title_full_unstemmed |
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. |
title_sort |
changes in proteome profile of peripheral blood mononuclear cells in chronic chagas disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004490 https://doaj.org/article/2c150de3294b493f9cceec800b7074a9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 2, p e0004490 (2016) |
op_relation |
http://europepmc.org/articles/PMC4769231?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004490 https://doaj.org/article/2c150de3294b493f9cceec800b7074a9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004490 |
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PLOS Neglected Tropical Diseases |
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10 |
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2 |
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e0004490 |
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