Study of electron transfer from cystein residues of proteolytic enzyme THIMET-Oligopeptidase to High Valence Intermediates of Mioglobin. Correlations to the cell oxidative stress.

• Grant number: 10/11504-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2010
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal Investigator: Iseli Lourenço Nantes Cardoso
• Grantee: Juliana Conrado Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Considering the high content of thiol groups present in TOP structure and the multiplicity of roles played by this enzyme, it is probable the involvement of these residues in the cell redox balance and signalization. In biological systems, thiols present a crucial role in the antioxidant defense network and are mediators of multiple metabolic, signaling and transcriptional processes. Thiol group present both in proteins and in low-molecular-mass peptides controls a considerable part of biological properties and functions involving enzyme catalysis, protein structure and redox-signalling pathways. On the other hand, the redox balance and signaling of cells is also related to another class of proteins: the hemeproteins. The participation of the hemeproteins in oxidative stress involves pro- and antioxidant actions. In this regard, it is well known the role played by hemeproteins as catalase, cytochrome c and mioglobin both in the combat and in the generation of free radical and excited species. More recently, another class of hemeproteins has gained interest and has been target of studies concerning their structure and functions: neuroglobins and cytoglobins. Neuroglobin and cytoglobin are two phylogenetically ancient globins which, in the absence of external ligands, exhibit hexacoordinate hemes with histidine residues at both proximal and distal coordination positions. Neuroglobin and cytoglobin are expressed at low levels in neuronal tissues and in all tissues investigated so far, respectively. Neuroglobin has been postulated to participate in the cellular defense against hypoxia but it is more probable to be a scavenger of reactive oxygen and nitrogen species that are generated following brain hypoxia. On the other hand, cytoglobin is upregulated upon hypoxia, and the O2-binding properties of this heme protein are consistent with a role in O2-requiring reactions, such as those catalysed by hydroxylases.