| Full text | |
| Author(s): |
Maluf, S. El Chamy
;
Hayashi, M. A. F.
;
Campeiro, J. D.
;
Oliveira, E. B.
;
Gazarini, M. L.
;
Carmona, A. K.
Total Authors: 6
|
| Document type: | Journal article |
| Source: | Toxicon; v. 208, p. 6-pg., 2022-01-26. |
| Abstract | |
Malaria is a parasitic infectious disease caused by Plasmodium sp, which was responsible for about 409 thousand deaths only in 2019. The clinical manifestations in patients with malaria, which may include fever and anemia and that can occasionally lead to the death of the host, are mainly associated to the asexual blood stage of parasite. The discovery of novel compounds active against stages of the intraerythrocytic cell cycle has been the focus of many researches seeking for alternatives to the control of malaria. The antimalarial effect of a native cationic polypeptide from the venom of a South American rattlesnake named crotamine, with ability of targeting and disrupting the acidic compartments of Plasmodium falciparum parasite, was previously described by us. Herein, we extended our previous studies by investigating the internalization and trafficking of crotamine in P. falciparum-infected erythrocytes at different blood-stages of parasites and periods of incubation. In addition, the effects of several pharmacological inhibitors in the uptake of this snake polypeptide with cell-penetrating properties were also assessed, showing that crotamine internalization was dependent on ATP generated via glycolytic pathway. We show here that crotamine uptake is blocked by the glycolysis inhibitor 2-deoxy-Dglucose, and the most efficient internalization is observed at trophozoite stage of parasite after at least 30 min of incubation. The present data provide important insights into biochemical pathway and cellular features determined by the parasite cycle, which may be underlying the internalization and effects of cationic antimalarials as crotamine. (AU) | |
| FAPESP's process: | 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/11683-8 - Study of the participation of proteases in pathological processes |
| Grantee: | Adriana Karaoglanovic Carmona |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/01107-7 - Study to optimize the use of crotamine as a theranostic in the therapy of human diseases: cancer, metabolic syndrome and renal dysfunction |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Research Projects - Thematic Grants |