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Urine proteomics as a non-invasive approach to monitor exertional rhabdomyolysis during military training

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Carneiro, Andreia ; Macedo-da-Silva, Janaina ; Santiago, Veronica Feijoli ; de Oliveira, Gilberto Santos ; Guimaraes, Thiago ; Mendonca, Clarissa Ferolla ; de Oliveira Branquinho, Jessica Lais ; Lucena, Cintia Verdan ; Osorio, Juliana ; Pernambuco, Eduardo ; Moreira, Josino Costa ; Pesquero, Joao Bosco ; Pereira, Marcos Dias ; Palmisano, Giuseppe
Total Authors: 14
Document type: Journal article
Source: JOURNAL OF PROTEOMICS; v. 258, p. 17-pg., 2022-04-30.

Exertional rhabdomyolysis (ERM), a condition often associated with strenuous exercise, a common practice in the military activities, can be defined as the process of injury and rupture of muscle cell membranes, with leakage of its components into the bloodstream. Creatine kinase (CK) has been used for ERM diagnosis, albeit several studies reported the discrepancy between CK levels and clinical signs or symptoms. In this study, we analyzed the biochemical profile of the blood, and the urinary proteome of ten marine soldiers in a special training course. The samples were collected in two periods, M1 and M2, which correspond to the lowest and highest CK levels during training, respectively. Quantitative urinary proteome profile of M1 and M2 showed changes in proteins involved in immune system and cell adhesion-related pathways after strenuous physical exercise. Changes in the abundance of several proteins was observed in individuals carrying genetic polymorphisms related to greater risk for muscle damage. A panel of proteins (CTSH, PIK3IP1, DEFB1, ITGB1, BCAN, and TNFRSF10C) presented high correlation with classical blood biochemical markers of ERM and AGT MET235Thr and ACE I/D polymorphisms. These proteins represent potential urine markers of muscle damage due to intense physical conditions such as military training activities. Significance: This study analyzed the blood and urine of a cohort of marine soldiers enrolled in a special training program including missions with low and high exposure to strenuous exercise. The biochemical blood profile, polymorphisms mapping and mass spectrometry-based analyses of the urinary pmteome was evaluated in such a controlled samples. A total of 226 urinary proteins associated to immune system, cell adhesion and redox homeostasis were significantly changes during ERM shedding lights on the disease pathogenesis. In particular, a panel of six proteins were associated to classical ERM markers and could be used as early non invasive biomarkers. (AU)

FAPESP's process: 18/13283-4 - Discovery of biomarkers of Chagas' disease in urine using mass spectrometry techniques
Grantee:Gilberto Santos de Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
Grantee:João Bosco Pesquero
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
Grantee:Giuseppe Palmisano
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
Grantee:Giuseppe Palmisano
Support Opportunities: Regular Research Grants
FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
Grantee:Giuseppe Palmisano
Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 21/00140-3 - Development and optimization of enrichment methods for arginylated proteins in complex biological matrices
Grantee:Janaína Macedo da Silva
Support Opportunities: Scholarships in Brazil - Doctorate