Wasp venom peptide as a new antichagasic agent
| Autor: | Katielle Albuquerque Freire, Dânya Bandeira Lima, Alice Maria Costa Martins, Vani Xavier Oliveira, Marcelo D. T. Torres, Ramon Róseo Paula Pessoa Bezerra de Menezes, Marília Lopes Monteiro |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Trypanosoma cruzi Wasps ved/biology.organism_classification_rank.species Apoptosis Wasp Venoms Peptide Toxicology 01 natural sciences Cell Line 03 medical and health sciences medicine Animals Nifurtimox Amastigote Trypanocidal agent Membrane Potential Mitochondrial chemistry.chemical_classification 0303 health sciences biology ved/biology 010604 marine biology & hydrobiology 030302 biochemistry & molecular biology Flow Cytometry biology.organism_classification Trypanocidal Agents Biochemistry Mechanism of action chemistry Nitroimidazoles Benznidazole medicine.symptom Peptides Reactive Oxygen Species Polybia paulista medicine.drug |
| Zdroj: | Toxicon. 181:71-78 |
| ISSN: | 0041-0101 |
| DOI: | 10.1016/j.toxicon.2020.04.099 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect