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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
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.
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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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