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

• Autores: Koo, Sue Jie; Spratt, Heidi M.; Soman, Kizhake V.; Stafford, Susan; Gupta, Shivali; Petersen, John R.; Zago, María Paola; Kuyumcu Martinez, Muge N.; Brasier, Allan R.; Wiktorowicz, John E.; Garg, Nisha Jain
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: S-NITROSYLATION; PROTEOMIC PROFILING; HEART FAILURE
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Koo, Sue Jie. University of Texas Medical Branch; Estados Unidos
Fil: Spratt, Heidi M.. University of Texas Medical Branch; Estados Unidos
Fil: Soman, Kizhake V.. University of Texas Medical Branch; Estados Unidos
Fil: Stafford, Susan. University of Texas Medical Branch; Estados Unidos
Fil: Gupta, Shivali. University of Texas Medical Branch; Estados Unidos
Fil: Petersen, John R.. University of Texas Medical Branch; Estados Unidos
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Kuyumcu Martinez, Muge N.. University of Texas Medical Branch; Estados Unidos
Fil: Brasier, Allan R.. University of Texas Medical Branch; Estados Unidos
Fil: Wiktorowicz, John E.. University of Texas Medical Branch; Estados Unidos
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos