MANGANESE REACTION MECHANISMS OF MESO-TETRAKIS PORPHYRINS WITH PEROXIDES OF MEMBRANE LIPIDS: CONTRIBUTIONS TO THE UNDERSTANDING OF THE BIOLOGICAL EFFECTS

• Grant number: 12/08322-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: June 07, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Iseli Lourenço Nantes Cardoso
• Grantee: Juliana Casares Araújo Chaves
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 08/04948-0 - Structure and reactivity of hemepeptides, hemeproteins and phorphyrins in homogeneous and heterogenoeus media: basic aspects and application in nanotechnology, AP.TEM

Abstract

Manganese porphyrins have been used in studies of the enzymology of antioxidant enzymes, superoxide dismutase (SOD) and catalase (MEUNIER et al. 1992; BATINIC-HABERLE 2002; SPASOJEVIC et al. 2003, DAY et al. 1997). Research on the antioxidant action of manganese porphyrins has focused on two approaches: chemical and electrochemical studies of porphyrins in homogeneous MnIIITMPyP buffered and studies on the antioxidant activity of these porphyrins in cells and subcellular organelles. Therefore, the first type of approach that aims to contribute to the understanding of mechanisms of biological action of MnIIITMPyP has been done in ways that differ greatly in biological systems while the second approach has been limited to reporting purposes, often attributing to the effects observed activities that are not expected for these porphyrin under physiological conditions, such as catalase activity. In this sense, our group has invested in studying the mechanisms of action of these porphyrins in biomimetic systems, but with an approach that is not limited to reporting purposes, but invests in elucidating the biochemical mechanisms responsible for the observed effects. In this project we intend to move in this investigative process, because the studies so far show that the biological activity (INADA et al. 2007; PESSOTO et al. 2009; ARAUJO et al. 2010; ARAUJO et al. 2011) these porphyrins are connected to a complex mechanism of cellular regulation and can both contribute to antioxidant activity as pro-oxidant, depending on the condition previous cell. Therefore in this project we propose to study the reaction mechanisms of MnIIITMPyP and MnIIITPPS4 with peroxides and lipids derived from mitochondrial and plasma membranes in situ and in liposomes with the composition of these membranes mimetics (PCPECL and PCPS) and correlate these mechanisms with the cellular redox state. For this, we will study these porphyrins such as the electrochemical processes using the technique of cyclic voltammetry, the intermediate radical species by reaction EPR technique, the possible formation of singlet oxygen that can lead to the formation of lipid peroxide, by means of a photomultiplier Infrared (PMT), and the oxidation promoted by free radical attack, which involves the formation of lipid peroxide and MDA and lipid hydroperoxide (LOOH) to ascertain the membrane damage. The biological effects on cells will be addressed through a cytometric rabbit aorta cells treated with these porphyrins.