Thermal Regulation of NADPH Oxidase in Macrophages

• Grant number: 25/04331-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Rafaelle Gomes da Fonseca
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In this project, we aim to investigate the activity mechanisms of NADPH oxidase (NOX), which has the primary function of catalyzing the production of reactive oxygen species (ROS), by exploring the overexpression of protein subunits in macrophages. We hypothesize that thermal stimulation regulates the enzymatic activity mechanisms of the gp47-phox, gp91-phox, and gp22-phox subunits. When grouped, these subunits compose the NADPH oxidase and are responsible for enzyme activation and functionality. Therefore, it is important to understand the correlation between temperature, the subunits that compose and ensure NOX activation, and the subsequent ROS production. ROS is a crucial inflammatory mediator that aids in eliminating invading microorganisms. This understanding will help us delve deeper into identifying the catalytic subunit of the NADPH oxidase complex, whether associated with the plasma membrane or the phagocytic vacuole of macrophages, that can amplify thermal modulation at a temperature mimicking hypothermia (referred to as inverse thermal modulation). This will enable us to better understand how macrophages can enhance their microbicidal activity under low-temperature conditions.