| Full text | |
| Author(s): |
Dempsey, Bianca
;
da Silva, Beatriz Pereira
;
Cruz, Litiele Cezar
;
Vileigas, Danielle
;
Silva, Amanda R. M.
;
da Silva, Railmara Pereira
;
Meotti, Flavia Carla
Total Authors: 7
|
| Document type: | Journal article |
| Source: | REDOX BIOLOGY; v. 82, p. 21-pg., 2025-05-01. |
| Abstract | |
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) | |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 18/14898-2 - Investigations of the redox processes in inflammatory response and associated pathologies |
| Grantee: | Flavia Carla Meotti |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 12/12663-1 - Singlet molecular oxygen and peroxides in chemical biology |
| Grantee: | Paolo Di Mascio |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 23/00995-4 - Development of metrics of quantitative proteomics capable of capturing the functional and compositional complexity of high-density lipoprotein |
| Grantee: | Graziella Eliza Ronsein |
| Support Opportunities: | Regular Research Grants |