Investigation on the redox modulation of inflammassome pathway: the pro-inflammatory effect of urate hydroperoxide

• Grant number: 13/23099-2
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2014
• Effective date (End): August 14, 2014
• Field of knowledge: Biological Sciences - Biochemistry
• Principal researcher: Flavia Carla Meotti
• Grantee: Sabrina Lopes Lira
• Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 11/18106-4 - Oxidation of uric acid by myeloperoxidase in inflammatory processes and the implications for cardiovascular disease, AP.JP

Abstract

Previous studies from our group demonstrated that the formation of urate hydroperoxide in inflammation is a key process in the maintenance of the inflammatory response. Our hypothesis is that the oxidation of redox-modulated proteins of the inflammasome cascade by urate hydroperoxide could explain the pro-inflammatory effect of soluble forms of uric acid. In this context, this project will investigate the effects of urate hydroperoxide on the inflammassome pathway, a multimeric complex that signalizes caspase 1 and interleukin 1 beta proteolysis. Therefore, this study aims to understand the molecular mechanisms in the inflammasome pathway and to understand the mechanisms by which urate, in a soluble form, act as a pro-inflammatory agent.