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Dinitrosyl iron complexes (DNICs): formation, reactivity, and implications for the physiopathology of nitric oxide

Grant number: 19/17483-0
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2020 - October 31, 2025
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Daniela Ramos Truzzi
Grantee:Daniela Ramos Truzzi
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Luis Eduardo Soares Netto ; Ohara Augusto ; Peter C. Ford

Abstract

Nitric oxide (NO) is a signaling molecule that plays roles in physiological and pathological processes. Among its capabilities, NO can act as an efficient cellular iron sequester forming dinitrosyl iron complexes (DNICs) and reducing oxidative stress from Fenton chemistry. This process may play important roles in a variety of pathologies associated with oxidative stress such as neurodegenerative diseases and cancer. DNICs are rapidly formed in cells exposed to NO, and are considered the most abundant NO-metabolite in intracellular media. Despite that, there is little information about the chemical and biological properties of cellular DNICs. Recently, we elucidated the mechanism of low molecular weight DNIC formation and verified that it can lead to biothiol nitrosation. DNICs involvement in S-nitrosothiol formation is relevant because the latter have been proposed to be involved in cell signaling. Therefore, this project aims to understand the formation mechanism, the biological composition and the reactivity of DNICs toward biological targets. To this end, the DNICs of cysteine, glutathione and specific thiol proteins involved in the antioxidant defense system (peroxiredoxins, thioredoxins and glutathione S-transferases) will be studied. The studies of the formation mechanism of high molecular weight DNICs aims to elucidate how NO is stored in biological systems and identify the macromolecules that participate in this process. In addition, the study of DNICs reactivity will provide information regarding the biological conditions in which DNICs can promote S-nitrosation reactions and participate in NO-signaling processes other than guanylate cyclase activation. (AU)