title: S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure.
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, 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.
authors.affiliation: Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
authors.forename: Sue-Jie
authors.identifier: 0000-0002-3305-9952
authors.initials: SJ
authors.lastname: Koo
authors.affiliation: Department Preventive Medicine and Community Health, UTMB, Galveston, TX 77555, USA; Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Spratt
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA.
authors.forename: Kizhake V
authors.identifier: 0000-0002-2578-7028
authors.initials: KV
authors.lastname: Soman
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA.
authors.forename: Susan
authors.identifier: 0000-0002-5648-6981
authors.initials: S
authors.lastname: Stafford
authors.affiliation: Department of Microbiology and Immunology, UTMB, Galveston, TX 77555, USA.
authors.forename: Shivali
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Petersen
authors.affiliation: Instituto de Patología Experimental, CONICET-UNSa, 4400 Salta, Argentina.
authors.forename: Maria P
authors.identifier: 0000-0002-5928-0508
authors.initials: MP
authors.lastname: Zago
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA.
authors.forename: Muge N
authors.initials: MN
authors.lastname: Kuyumcu-Martinez
authors.affiliation: Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA; Department of Internal Medicine-Endocrinology, UTMB, Galveston, TX 77555, USA.
authors.forename: Allan R
authors.identifier: 0000-0002-5012-4090
authors.initials: AR
authors.lastname: Brasier
authors.affiliation: Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA; Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA; Institute for Human Infections and Immunity, UTMB, Galveston, TX 77555, USA.
authors.forename: John E
authors.identifier: 0000-0002-9269-2336
authors.initials: JE
authors.lastname: Wiktorowicz
authors.affiliation: Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA; Department of Microbiology and Immunology, UTMB, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, UTMB, Galveston, TX 77555, USA.
authors.forename: Nisha Jain
authors.identifier: 0000-0002-3453-2369
authors.initials: NJ
authors.lastname: Garg