| Full text | |
| Author(s): |
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
Total Authors: 7
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Toxicon; v. 181, p. 71-78, JUL 15 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 14/04507-5 - Biological applications of new antimicrobial peptides |
| Grantee: | Marcelo Der Torossian Torres |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 17/03046-2 - Biologically active peptides against pathogenic microorganisms and cancer cells |
| Grantee: | Vani Xavier de Oliveira Junior |
| Support Opportunities: | Regular Research Grants |