Damage to biomolecules caused by redox systems: study of mechanisms and development of sensitive biomarkers

• Grant number: 06/56663-4
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2006
• End date: April 30, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marisa Helena Gennari de Medeiros
• Grantee: Marisa Helena Gennari de Medeiros
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

A very large body of studies has focused on the role of redox-dependent mechanisms in a broad variety of disease conditions including cancer. A basic and prime drawback that prevents a better understanding of redox pathophysiology is the overall difficulty and the almost lack of availability of adequate indexes to quantitatively assess the redox status of in vivo systems, including cells, tis sues and whole organisms. Redox processes induce direct or indirect damage to biomolecules. It is well known that lipid peroxidation products as acrolein, crotonaldehyde, trans-2-hexenal, trans, trans-2,4-decadienal and, trans-4-hydroxy-2-nonenal can alkylate DNA and proteins producing adducts. The ability of such molecules to react with biological targets and exert cytotoxic effects is only beginning to be studied. The aim of the present study is to investigate the mechanisms and the products of redox damage to biomolecules by ultra sensitive methods. The levels of these adducts will be detected and quantified in vitro, test tubes and cell cultures, and in model systems, transgenic rats with mutant SODI and rats exposed to urban air pollution. The possible mechanisms of adduct formation and the effect of antioxidants will be also investigated. (AU)