Intracellular localization of NOX isoforms in pancreatic beta cells after exposure to pro-inflammatory cytokines

• Grant number: 23/03932-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fernanda Ortis
• Grantee: Paulo Henrique Coelho Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Reactive Oxygen Species (ROS) have an important role as physiological signaling elements of the pancreatic beta cells, as they are relevant in the Glucose-Stimulated Insulin Secretion. NOX enzymes (NADPH Oxidase) are part of a 7-member family in the human genome and they are generators of ROS. Because of its highly reactive nature, which ispotentially dangerous to the cell components, ROS generation needs to occur next to its signalling targets; otherwise, the cell can suffer from oxidative stress. Beta cells disfunction and death, that occurs during the development of the different types of Diabetes mellitus (DM), is responsible for insufficient insulin secretion, which leads to cronic hyperglicemia with consequent damage to different organs. In the type 1 DM autoimmune destruction of beta cells occurs. In this process, the pro-inflammatory enviroment of the pancreatic islets has cytokines such as IL-1², IFN³ and TNF, which contribute to beta cell damage. These molecules induce beta cells death through different mechanisms, recent studies from our group have shown that expression of NOX enzymes can be induced by these cytokines. Inaddition, it is possible that pro-inflammatory cytokines modulate NOX enzymes localizationin beta cells. Therefore, we aim to characterize the intracellular localization of the differentNOX isoforms in beta cells and its modulation after exposure to pro-inflammatory cytokines.This knowledge can help to better understand how the pro-inflammatory islet environment,present during DM1 development, can modulate such enzymes, and from that infer what disturbances to the redox signaling occurs. This is extremely important as it allows the discovery of therapeutic targets against DM1 development.