Involvement of tioredoxin-interacting protein (TXNIP) in the relationship between autophagy and inflammasome

• Grant number: 18/13166-8
• Support Opportunities: Research Grants - Visiting Researcher Grant - Brazil
• Start date: October 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Flavia Carla Meotti
• Grantee: Flavia Carla Meotti
• Visiting researcher: Alcir Luiz Dafre
• Visiting researcher institution: Universidade Federal de Santa Catarina (UFSC). Centro de Ciências Biológicas, Brazil
• 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

The research group led by Prof. Meotti is interested to understand how the oxidants generated during the inflammatory oxidative burst modulate inflammatory cells and the surrounding cells response. The aim is to understand the role of the redox modulation in the maintenance, propagation and resolution of inflammation, mainly in chronic pathologies, describing the biochemical mechanisms of disease maintenance/progression to pave the way for appropriated therapeutic intervention. One of the main pro-inflammatory pathway in macrophages is the inflammasome complex. The formation of this complex is triggered by a conjunction of stimuli, including the increase of oxidants, culminating with the oligomerization of cytosolic proteins, like the thioredoxin-interacting protein (Txnip). The Txnip interacts with thioredoxin (Trx) but also with other proteins and can modulate autophagy. Autophagy is triggered by cellular stress and is important for cell survival; therefore, it could be a mechanism of inflammatory cell resilience and inflammation preservation. In this context, this research project will investigate the relationship between inflammasome activation and autophagy, focusing on the molecular mechanisms dependent on redox modulation and cell survival. Prof. Dafre's expertise in autophagy signaling will be very helpful to understand the mechanisms by which Txnip sustains oxidants production in the cell and the inflammasome redox modulation during autophagy. (AU)