Wasp venom peptide as a new antichagasic agent

Autor(es)

Freire, Katielle Albuquerque ^[1] ; Torres, Marcelo Der Torossian ^{[1, 2, 3, 4]} ; Lima, Danya Bandeira ^[5] ; Monteiro, Marilia Lopes ^[5] ; Pessoa Bezerra de Menezes, Ramon Roseo Paula ^[5] ; Costa Martins, Alice Maria ^[5] ; Oliveira Jr, Vani Xavier

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humans, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 - USA

^[3] Univ Penn, Perelman Sch Med, Penn Inst Computat Sci, Inst Biomed Informat, Inst Translat Med & Therapeut, Machine Biol Grp, De, Philadelphia, PA 19104 - USA

^[4] Univ Penn, Perelman Sch Med, Penn Inst Computat Sci, Dept Microbiol, Inst Translat Med & Therapeut, Machine Biol Grp, In, Philadelphia, PA 19104 - USA

^[5] Univ Fed Ceara, Fac Farm, Dept Anal Clin & Toxicol, BR-60430372 Fortaleza, Ceara - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 181, p. 71-78, JUL 15 2020.
• Citações Web of Science: 0

Resumo

Chagas disease is caused by Trypanosoma cruzi and affects approximately 10 million people a year worldwide. The only two treatment options, benznidazole and nifurtimox, have low efficacy and high toxicity towards human cells. Mastoporan peptide (MP) a small cationic AMP from the venom of the wasp Polybia paulista has been reported as a potent trypanocidal agent. Thus, we evaluated the antichagasic effect of another AMP from the venom of the same wasp Polybia paulista, polybia-CP (ILGTILGLLSKL-NH2), and investigated its mechanism of action against different stages of the trypanosomal cells life cycle. Polybia-CP was tested against the epimastigote, trypomastigote and amastigote forms of the T. cruzi Y strain (benznidazole-resistant strain) and inhibited the development of these forms. We also assessed the selectivity of the AMP against mammalian cells by exposing LLC-MK2 cells to polybia-CP, the peptide presented a high selectivity index (>106). The mechanism of action of polybia-CP on trypanosomal cells was investigated by flow cytometry, scanning electron microscopy (SEM) and enzymatic assays with T. cruzi GAPDH (tcGAPDH), enzyme that catalyzes the sixth step of glycolysis. Polybia-CP induced phosphatidylserine exposure, it also increased the formation of reactive species of oxigen (ROS) and reduced the transmembrane mitochondrial potential. Polybia-CP also led to cell shrinkage, evidencing apoptotic cell death. We did not observe the inhibition of tcGAPDH or autophagy induction. Altogether, polybia-CP has shown the features of a promising template for the development of new antichagasic agents. (AU)

• Processo FAPESP: 14/04507-5 - Aplicações biológicas de novos peptídeos antimicrobianos
• Beneficiário: Marcelo Der Torossian Torres
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/03046-2 - Peptídeos biologicamente ativos em micro-organismos patogênicos e em células tumorais
• Beneficiário: Vani Xavier de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular