Table of Contents
International Journal of Proteomics
Volume 2016, Article ID 1384523, 19 pages
http://dx.doi.org/10.1155/2016/1384523
Research Article

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure

1Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA
2Department Preventive Medicine and Community Health, UTMB, Galveston, TX 77555, USA
3Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA
4Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA
5Department of Microbiology and Immunology, UTMB, Galveston, TX 77555, USA
6Instituto de Patología Experimental, CONICET-UNSa, 4400 Salta, Argentina
7Department of Internal Medicine-Endocrinology, UTMB, Galveston, TX 77555, USA
8Institute for Human Infections and Immunity, UTMB, Galveston, TX 77555, USA

Received 30 January 2016; Revised 7 April 2016; Accepted 16 May 2016

Academic Editor: Christoph H. Borchers

Copyright © 2016 Sue-jie Koo et al. 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.

Abstract

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, /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, ). 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.