Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease

• Autores: Garg, Nisha Jain; Soman, Kizhake V.; Zago, María Paola; Koo, Sue-Jie; Spratt, Heidi; Stafford,Susan; Blell, Zinzi N.; Gupta, Shivali; Nuñez Burgos, Julio; Barrientos, Natalia Mariel; Brassier, Allan R.; Wiktorowicz, John E.
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: PROTEOME; CHRONIC CHAGAS DISEASE; HUMAN PBMCs
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30–40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction. Protein samples were labeled with BODIPY FL-maleimide (dynamic range: > 4 orders of magnitude, detection limit: 5 f-mol) and resolved by two-dimensional gel electrophoresis (2D-GE). After normalizing the gel images, protein spots that exhibited differential abundance in any of the two groups were analyzed by mass spectrometry, and searched against UniProt human database for protein identification. We found 213 and 199 protein spots (fold change: |≥ 1.5|, p< 0.05) were differentially abundant in C/A and C/S individuals, respectively, with respect to N/H controls. Ingenuity Pathway Analysis (IPA) of PBMCs proteome dataset identified an increase in disorganization of cytoskeletal assembly and recruitment/activation and migration of immune cells in all chagasic subjects, though the invasion capacity of cells was decreased in C/S individuals. IPA predicted with high probability a decline in cell survival and free radical scavenging capacity in C/S (but not C/A) subjects. The MYC/SP1 transcription factors that regulate hypoxia and oxidative/inflammatory stress were predicted to be key targets in the context of control of Chagas disease severity. Further, MARS-modeling identified a panel of proteins that had >93% prediction success in classifying infected individuals with no disease and those with cardiac involvement and LV dysfunction. In conclusion, we have identified molecular pathways and a panel of proteins that could aid in detecting seropositive individuals at risk of developing cardiomyopathy.
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos
Fil: Soman, Kizhake V.. 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: Koo, Sue-Jie. University of Texas Medical Branch; Estados Unidos
Fil: Spratt, Heidi. University of Texas Medical Branch; Estados Unidos
Fil: Stafford,Susan. University of Texas Medical Branch; Estados Unidos
Fil: Blell, Zinzi N.. University of Texas Medical Branch; Estados Unidos
Fil: Gupta, Shivali. University of Texas Medical Branch; Estados Unidos
Fil: Nuñez Burgos, Julio. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Barrientos, Natalia Mariel. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Brassier, Allan R.. University of Texas Medical Branch; Estados Unidos
Fil: Wiktorowicz, John E.. University of Texas Medical Branch; Estados Unidos