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Mapping adducts generated by endogenous and exogenous aldehydes: use as biomarkers of redox stress

Grant number: 11/19362-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2011
Effective date (End): September 30, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Marisa Helena Gennari de Medeiros
Grantee:Vanderson da Silva Bispo
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo, SP, Brazil
Associated research grant:11/10048-5 - Mapping adducts generated by endogenous and exogenous aldehydes: use as biomarkers of redox stress, AP.TEM

Abstract

Several processes including oxidative metabolism, inflammation, exposure to physical agents such as UV light and ionizing radiation produce reactive intermediates capable of producing damage to biomolecules. The increase in these lesions has been linked with a variety of diseases as cancer and aging. In recent years there has been a major advance in available technology, especially mass spectrometry, allowing ultra-sensitive quantitative studies of changes in DNA, proteins and other biomolecules. This breakthrough has generated a large research effort focused on identifying the mechanisms of formation, interaction and consumption of reactive intermediates. This project aims to study the mechanisms of damage to biomolecules caused by endogenous and exogenous reactive aldehydes using modern and ultra-sensitive technology. Studies with cells and transgenic animal model for amyotrophic lateral sclerosis will be conducted as well as damage to biomolecules caused by exogenous aldehydes generated by urban pollution, cigarette smoke, and protein-energy malnutrition in animal models and human blood and urine. Several modifications to biomolecules are often formed in human tissues after exposure to reactive aldehydes, a systematic investigation of these lesions is needed to identify which lesion is the most critical in each of the situations studied. A methodology to quantify multiple lesions in DNA and glutathione, route of detoxification of these aldehydes, using HPLC/MS/MS will be performed. We emphasize that our laboratory has different standards of nucleosides and glutathione modified by aldehydes, characterized, in recent years, by our group and others. A systematic quantification of these lesions can provide important information about the pathophysiological role of these aldehydes as well as identifying potential markers of redox stress in vivo. (AU)