Unraveling the effects of uric acid on endothelial cells: A global proteomic study

Autor(es)

Dempsey, Bianca ; da Silva, Beatriz Pereira ; Cruz, Litiele Cezar ; Vileigas, Danielle ; Silva, Amanda R. M. ; da Silva, Railmara Pereira ; Meotti, Flavia Carla

• Tipo de documento: Artigo Científico
• Fonte: REDOX BIOLOGY; v. 82, p. 21-pg., 2025-05-01.

Resumo

This work aims to understand how normouricemic levels of uric acid can induce endothelial dysfunction seeking global proteomic alterations in Human Umbilical Vein cells (HUVEC). It reveals significant alterations in redoxsensitive and antioxidant proteins, chaperones, and proteins associated with cell migration and adhesion in response to uric acid exposure. Monitoring cellular oxidation with the roGFP2-Grx1 probe proved increased oxidation levels induced by uric acid, which can be attenuated by peroxidasin (PXDN) inhibition, suggesting a regulatory role for PXDN in mitigating oxidative stress induced by uric acid. As a consequence of uric acid oxidation and the formation of reactive intermediate, we identified adducts in proteins (+140 kDa) in a novel post-translation modification named uratylation. Increased misfolded protein levels and p62 aggregation were also found, indicating disturbances in cellular proteostasis. Furthermore, uric acid promoted monocyte adhesion and upregulated ICAM and VCAM protein levels, implicating a pro-inflammatory response in endothelial cells. These findings provide critical insights into the molecular mechanisms underlying vascular damage associated with uric acid. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/14898-2 - Processos redox na inflamação e o seu papel sobre doenças inflamatórias
• Beneficiário: Flavia Carla Meotti
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 12/12663-1 - Oxigênio singlete e peróxidos em química biológica
• Beneficiário: Paolo Di Mascio
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 23/00995-4 - Desenvolvimento de métricas de proteômica quantitativa capazes de capturar a complexidade funcional e composicional da lipoproteína de alta densidade
• Beneficiário: Graziella Eliza Ronsein
• Modalidade de apoio: Auxílio à Pesquisa - Regular