The signaling role of tryptophan tricyclic hidroperoxides in smooth cells of vascular epithelium

• Grant number: 19/16259-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2020
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Paolo Di Mascio
• Grantee: Felipe Jun Fuzita
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

In 2008, two isomeric tryptophan hydroperoxides (cis and trans WOOH) were characterized by our group as the main singlet oxygen tryptophan oxidation products. These peroxides break down into alcohols, formylkynurenine and kynurenine. In 2010, it was proposed that kynurenine is a relaxing endothelial factor that aids in controlling blood pressure. Under inflammatory conditions, the enzyme indoleamine 2,3-dioxygenase (Ido), expressed in endothelial cells would be responsible for the generation of kynurenine. Recently, it was observed that Ido generates singlet oxygen in the presence of hydrogen peroxide, and at the active site stereo-selectively oxidizes tryptophan generating cis-WOOH. Thus, kynurenine was in fact a byproduct of cis-WOOH degradation, which is the actual responsible for the signaling role that triggers arterial relaxation in inflammatory conditions. Preliminary studies suggest that cis-WOOH signaling activity appears to be dependent on the cysteine 42 (Cys42) oxidation of protein kinase G1± (PKG1±). However, little is known about the cellular targets of this peroxide, and the mechanisms triggered by its action. Using tools of redox proteomics, classical biochemistry, bioinformatics and statistics, this project aims to clarify the signaling role of cis-WOOH in smooth cells of vascular epithelium. (AU)