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S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure
Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007369/ https://www.ncbi.nlm.nih.gov/pubmed/27635260 http://dx.doi.org/10.1155/2016/1384523 |
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author | Koo, Sue-jie Spratt, Heidi M. Soman, Kizhake V. Stafford, Susan Gupta, Shivali Petersen, John R. Zago, Maria P. Kuyumcu-Martinez, Muge N. Brasier, Allan R. Wiktorowicz, John E. Garg, Nisha Jain |
author_facet | Koo, Sue-jie Spratt, Heidi M. Soman, Kizhake V. Stafford, Susan Gupta, Shivali Petersen, John R. Zago, Maria P. Kuyumcu-Martinez, Muge N. Brasier, Allan R. Wiktorowicz, John E. Garg, Nisha Jain |
author_sort | Koo, Sue-jie |
collection | PubMed |
description | Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change | ≥1.5|, p ≤ 0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes' migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identified a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profiling identified ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top differentially abundant and S-NO-modified proteins, and these proteins were verified by Western blotting and ELISA in different set of HF subjects. We conclude that differential abundance and S-NO modification of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure. |
format | Online Article Text |
id | pubmed-5007369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-50073692016-09-15 S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure Koo, Sue-jie Spratt, Heidi M. Soman, Kizhake V. Stafford, Susan Gupta, Shivali Petersen, John R. Zago, Maria P. Kuyumcu-Martinez, Muge N. Brasier, Allan R. Wiktorowicz, John E. Garg, Nisha Jain Int J Proteomics Research Article Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change | ≥1.5|, p ≤ 0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes' migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identified a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profiling identified ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top differentially abundant and S-NO-modified proteins, and these proteins were verified by Western blotting and ELISA in different set of HF subjects. We conclude that differential abundance and S-NO modification of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure. Hindawi Publishing Corporation 2016 2016-08-18 /pmc/articles/PMC5007369/ /pubmed/27635260 http://dx.doi.org/10.1155/2016/1384523 Text en Copyright © 2016 Sue-jie Koo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Koo, Sue-jie Spratt, Heidi M. Soman, Kizhake V. Stafford, Susan Gupta, Shivali Petersen, John R. Zago, Maria P. Kuyumcu-Martinez, Muge N. Brasier, Allan R. Wiktorowicz, John E. Garg, Nisha Jain S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title | S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title_full | S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title_fullStr | S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title_full_unstemmed | S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title_short | S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure |
title_sort | s-nitrosylation proteome profile of peripheral blood mononuclear cells in human heart failure |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007369/ https://www.ncbi.nlm.nih.gov/pubmed/27635260 http://dx.doi.org/10.1155/2016/1384523 |
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