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Evaluation of damage pathway signs and cytokines inflammatory induction in the presence of BthTX-I toxin isolated from Bothrops jararacussu venom.

Grant number: 10/03243-3
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2012
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Suely Vilela
Grantee:Cássio Prinholato da Silva
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The activities of animal toxins in different biological mechanisms have contributed significantly to the development of new drugs, as well as the adoption of more effective therapeutic strategies in various human diseases. However, although the molecular basis of action from these toxins are still poorly understood, it is known that the effects from these toxins undertake the cycle of certain biological activities such as apoptosis, cell cycle, inflammation and tissue necrosis. Given this information, this project aims to investigate the action of the BthTX-I, a toxin purified from Bothrops jararacussu snake venom, in human tumor lines HL-60 (human promyelocytic leukemia) and HepG2 (human hepatocellular liver carcinoma) and animals tumor cell lines B16F10 (murine melanoma) and PC12 (pheochromocytoma of the rat adrenal medulla). Thus, we will analyze the induction of apoptotic cells by flow cytometry assay and DNA fragmentation. The performance of BthTX-I will be evaluated on the cell cycle. In sequence, will be checked routes of BthTX-I in front studies of gene expression, characterizing the process of apoptosis mediated by pro-apoptotic genes TP53 and BAX and the anti-apoptotic gene Bcl-2, assayed by Real Time-PCR. In another approach, we will assess the immunological potential of this protein in the induction of inflammatory cytokines and factor promotion (TNF-± and IL-8) by ELISA methodology with different concentrations of BthTX-I. The data generated in this work will contribute to better understanding the effects of action from this toxin, thereby providing important tools for the development of more targeted therapeutic strategies, as well as the possibility of discovering a new drug.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Cássio Prinholato da. Avaliação das vias de sinalização de danos e indução de citocinas inflamatórias na presença da toxina BthTX-I, isolada da peçonha de Bothrops jararacussu. 2012. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

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