Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni)Click to copy article linkArticle link copied!
- Anderson DemateiAnderson DemateiCenter for Tropical Medicine (NMT), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by Anderson Dematei
- Samuel Ribeiro CostaSamuel Ribeiro CostaLaboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, BrazilMore by Samuel Ribeiro Costa
- Daniel C. MoreiraDaniel C. MoreiraResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by Daniel C. Moreira
- Eder Alves BarbosaEder Alves BarbosaResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilLaboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, BrazilMore by Eder Alves Barbosa
- Lucas F. Friaça AlbuquerqueLucas F. Friaça AlbuquerqueResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by Lucas F. Friaça Albuquerque
- Andreanne G. VasconcelosAndreanne G. VasconcelosResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by Andreanne G. Vasconcelos
- Tiago NascimentoTiago NascimentoResearch Center on Biodiversity and Biotechnology (Biotec), Parnaiba Delta Federal University, Parnaíba 64202-020, BrazilMore by Tiago Nascimento
- Pedro Costa SilvaPedro Costa SilvaResearch Center on Biodiversity and Biotechnology (Biotec), Parnaiba Delta Federal University, Parnaíba 64202-020, BrazilMore by Pedro Costa Silva
- Amandda É. Silva-CarvalhoAmandda É. Silva-CarvalhoLaboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasília, Brasília 70910-900, BrazilMore by Amandda É. Silva-Carvalho
- Felipe Saldanha-AraújoFelipe Saldanha-AraújoLaboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasília, Brasília 70910-900, BrazilMore by Felipe Saldanha-Araújo
- Mariana Camargo Silva ManciniMariana Camargo Silva ManciniMultidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, BrazilMore by Mariana Camargo Silva Mancini
- Luis Gustavo Saboia PonteLuis Gustavo Saboia PonteMultidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, BrazilMore by Luis Gustavo Saboia Ponte
- Rosangela Maria Neves BezerraRosangela Maria Neves BezerraMultidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, BrazilMore by Rosangela Maria Neves Bezerra
- Fernando Moreira SimabucoFernando Moreira SimabucoMultidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, BrazilMore by Fernando Moreira Simabuco
- Augusto Batagin-NetoAugusto Batagin-NetoInstitute of Science and Engineering, São Paulo State University (UNESP), Itapeva, São Paulo 01049-010, BrazilMore by Augusto Batagin-Neto
- Guilherme BrandGuilherme BrandLaboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, BrazilMore by Guilherme Brand
- Tatiana Karla S. BorgesTatiana Karla S. BorgesResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by Tatiana Karla S. Borges
- Peter EatonPeter EatonLAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4099-002, PortugalThe Bridge, Joseph Banks Laboratories, School of Chemistry, University of Lincoln, Lincoln LN6 7TS, U.K.More by Peter Eaton
- José Roberto S. A. Leite*José Roberto S. A. Leite*Phone: +556131071891. E-mail: [email protected]; [email protected]Center for Tropical Medicine (NMT), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilResearch Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, BrazilMore by José Roberto S. A. Leite
Abstract

In this study, we report the isolation, characterization, and synthesis of the peptide BmT-2 belonging to the tryptophyllins family, isolated from the venom of the snake Bothrops moojeni. This is the first time a tryptophyllin is identified in snake venom. We tested whether BmT-2 had cytotoxic effects and antioxidant activity in a set of experiments that included both in vitro and cell-based assays. BmT-2 presented a radical scavenging activity toward ABTS• and AAPH-derived radicals. BmT-2 protected fluorescein, DNA molecules, and human red blood cells (RBCs) from free radicals generated by the thermal decomposition of AAPH. The novel tryptophyllin was not toxic in cell viability tests, where it (up to 0.4 mg/mL) did not cause hemolysis of human RBCs and did not cause significant loss of cell viability, showing a CC50 > 1.5 mM for cytotoxic effects against SK-N-BE(2) neuroblastoma cells. BmT-2 prevented the arsenite-induced upregulation of Nrf2 in Neuro-2a neuroblasts and the phorbol myristate acetate-induced overgeneration of reactive oxygen species and reactive nitrogen species in SK-N-BE(2) neuroblastoma cells. Electronic structure calculations and full atomistic reactive molecular dynamics simulations revealed the relevant contribution of aromatic residues in BmT-2 to its antioxidant properties. Our study presents a novel peptide classified into the family of the tryptophyllins, which has been reported exclusively in amphibians. Despite the promising results on its antioxidant activity and low cytotoxicity, the mechanisms of action of BmT-2 still need to be further elucidated.
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