CARNOSINE PROTECTION IN CARDIAC ISCHEMIC EVENTS: A FERROPTOSIS APPROACH

• Grant number: 24/17409-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 01, 2024
• End date: August 26, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marisa Helena Gennari de Medeiros
• Grantee: Bianca Scigliano Vargas
• Supervisor: Jose Pedro Friedmann Angeli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Julius-Maximilians-Universität Würzburg (JMU), Germany
• Associated to the scholarship: 19/24899-9 - Role of reactive aldehydes in cigarette smoke DNA damage and detoxification mechanisms in lungs and heart: development of urinary biomarkers of exposure, BP.DD

Abstract

The present proposal addresses an internship at the Rudolf Virchow Center at the University of Würzburg through the BEPE/FAPESP Ph.D. program for 6 months. The aim of the project is to pursue the relationship between the still unexplained carnosine (¿-alanyl-L-histidine) protection of cardiac cells during ischemia/reperfusion injury and its recently discovered role in avoiding ferroptosis. Different cell types (both wild-type and modified lines) will be cultured in presence and absence of carnosine, exposed to I/R protocol and ferroptosis markers will be assessed. Recent literature indicates that carnosine exhibits a protective role in cardiac ischemic events, but the underlying molecular mechanisms remain unclear. Other than being easily supplemented in the diet, this dipeptide shows a range of functions (e.g. metal chelation, intracellular pH buffering, glycation protection and aldehyde sequestering). Ferroptosis is a regulated form of cell death characterized by iron-driven accumulation of lipid peroxides that relies in distinct biochemical alterations, such as glutathione depletion and inactivation of glutathione peroxidase 4 (GPX4). Through a still unknown mechanism, carnosine has been shown to help renal cells evade ferroptosis. In this project, we will be able to employ molecular biology techniques to correlate both cardiac I/R injury and ferroptosis to better understand the role carnosine plays in this potentially fatal condition. In this context, Prof. Angeli's group is considered a reference in the field of ferroptosis, enabling us to unravel the mechanisms by which carnosine is protective against I/R injury.