Investigation of Modifications in Biomolecules Induced by Endogenous Aldehydes

• Grant number: 24/10532-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marisa Helena Gennari de Medeiros
• Grantee: Stephanie Yaciche Ferreira
• 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

Unsaturated aldehydes are reactive species capable of reacting with lipids, proteins, and DNA. Various pieces of evidence point to the involvement of reactive aldehydes in the progression of pathologies such as cardiovascular diseases, arteriosclerosis, and neurodegenerative diseases. A central goal of our project is to study the chemical reactivity of redox intermediates in biological environments and the consequent changes in the structure and function of biomolecules, to understand how each redox intermediate reacts with specific biomolecules and the resulting effects, which are essential for the development of biomarkers and antioxidants. Our group investigates the mechanisms of formation, detoxification, and reaction with biomolecules of both endogenous and exogenous reactive aldehydes in redox stress situations, such as in pathologies like amyotrophic lateral sclerosis (ALS) and exposure to urban pollution. One detoxification mechanism of these aldehydes is through conjugation with carnosine or glutathione. We observed that the supplementation of ALS SODG93A transgenic animals with carnosine, via oral administration, resulted in a delay in weight loss due to muscle atrophy and an increase in the animals' survival. The present project aims to investigate the role of endogenous aldehydes in the formation of DNA lesions in this process and to verify the possible effect of carnosine in the detoxification of these adducts. Expanding the study on the detoxification of adducts, in addition to studies with rat muscle, the project also aims to quantify these adducts in cultured cells exposed to redox stress.