Study of intracellular signaling pathways involved in the cytoprotective activity Lopap (Lonomia obliqua prothrombin activator protease) and peptides derived

• Grant number: 12/24708-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2013
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Cicilia de Carvalho
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The Lopap has been appointed as one of the major toxins from the venom Lonomia obliqua, and possibly one of the responsible for the consumption coagulopathy observed in victims of poisoning by contact with this animal. It has been shown that the has Lopap cytoprotective activity in different cell lines. This molecule is currently classified as a member of the family of lipocalins, since its primary sequence shows a similarity 20-59% with these proteins and the presence of three fields which define the characteristic lipocalins. From these three domains present in the primary structure of Lopap, peptides were synthesizedamong them the so called P2 and P4, related to motifi 2, which showed a cytoprotective effect on endothelial cells to apoptosis induced by serum deprivation. Furthermore the P4 peptide induced increased expression of extracellular matrix proteins such as collagen and fibronectin, and can aid in tissue remodeling. A sequence of seven amino acids common among peptides P2 and P4 was identified as sequence-signature of lipocalins. However, it is still unclear how the lipocalins participate in the modulation cell. Thus the aim of this study is to investigate molecular targets and intracellular signaling pathways involved in the induction of cell survival both lopap as the original P4 and its derived peptides, thus contributing to the understanding of its mechanism of action and molecular properties essential for the recognition process at the molecular level.