Advanced search
Start date

Effect of urate hydroperoxide on the oxidation extracellular surface thiol-proteins in endothelial cells and the relation with cellular spreading, adhesion and proliferation

Grant number: 20/01394-6
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2020
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Flavia Carla Meotti
Grantee:Danielle Fernandes Vileigas
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:18/14898-2 - Investigations of the redox processes in inflammatory response and associated pathologies, AP.JP2


We have demonstrated that the oxidation of uric acid occurs at the early events of Atherosclerosis and could be associated to vascular damage and progression of the disease. Oxidation of uric acid by peroxidases generates urate free radical and urate hydroperoxide. Urate hydroperoxide efficiently oxidizes the recombinant thiol-protein PDI (Protein Disulfide Isomerase), an important protein involved in vascular remodeling, platelet activation, aggregation, thrombosis and integrin signaling. We also demonstrated that urate hydroperoxide oxidizes PDI at the extracellular surface of endothelial (HUVEC) cells. It is possible that urate hydroperoxide oxidizes other cell surface thiol-proteins either directly or indirectly through protein disulfide exchange and this might be also involved in vascular remodeling. To identify which proteins are being oxidizing and interfering in the cellular adhesion to the extracellular matrix, a global study of extracellular cell surface redox proteomics need to be performed. The redox alterations on endothelial cell surface proteins will be correlated with morphological and functional activities of the cell, including cell spreading, adhesion and migration. Specific proteins involved in these processes will be identified by fluorescence microscopy. These analyses will elucidate the role of thiol-protein redox modification in the interaction with extracellular matrix and with vascular remodeling. This is highly relevant in the field, since we still don't know how much physiological oxidants can interfere in these cellular process. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Please report errors in scientific publications list by writing to: