Relevance of T. cruzi mitochondrial and cytosolic tryparedoxin peroxidase to the protection of cells against hydroperoxides mediated damage

• Grant number: 07/07458-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2008
• End date: March 31, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Fernanda Ramos Gadelha
• Grantee: Fernanda Ramos Gadelha
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Cytosolic tryparedoxin peroxidase (TcCPx) is an antioxidant protein, member of a unique enzymatic cascade for hydroperoxide detoxification restricted to trypanosomatids. This cascade is different from any hydroperoxide detoxification system present in the mammalian host, and offers options for the development of a more specific therapy. Another tryparedoxin peroxidase (TcMPx) was identified in the mitochondria, along with other cascade components, suggesting that or this compartment has all the components described for the cytosol, or there is a complementary role among cytosol and mitochondria in order to protect the parasite against hydroperoxide mediated damage.Since TcMPx identification in 2000, there has been no description in the literature of its role and possible cooperation with the cytosolic counterpart, in T. cruzi protection against oxidative stress. As an approach to investigate the function of these peroxiredoxins, T. cruzi epimastigotes overexpressing TcMPx or TcCPx will be evaluated for their resistance to hydrogen peroxide (H2O2) or t-butylhydroperoxide treatment as well to the increase in the hydroperoxide tone in mitochondria. Besides this approach, we will study the mRNA and protein levels of these enzymes, in two strains with different resistance to oxidative stress submitted to the treatments described above. Mitochondrial bioenergetics and the involvement of peroxide-removing enzymes in the protection of mitochondria against calcium-induced damage will be evaluated. (AU)