| Full text | |
| Author(s): |
Dias, Barbara K. M.
;
Nakabashi, Myna
;
Alves, Marina Rangel Rodrigues
;
Portella, Danielle Pagliaminuto
;
dos Santos, Benedito Matheus
;
Almeida, Fahyme Costa da Silva
;
Ribeiro, Ramira Yuri
;
Schuck, Desiree C.
;
Jordao, Alessandro Kappel
;
Garcia, Celia R. S.
Total Authors: 10
|
| Document type: | Journal article |
| Source: | Journal of Pineal Research; v. 69, n. 3, p. 17-pg., 2020-08-07. |
| Abstract | |
Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malariaPlasmodium falciparumthat lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia inP. falciparumand blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparumcell cycle with IC(50)9.76 mu M +/- 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT)P. falciparum(3D7) in 72 hours culture assays with the IC(50)values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials. (AU) | |
| FAPESP's process: | 18/07177-7 - EMU concedido no processo 2011/51295-5: image system |
| Grantee: | Célia Regina da Silva Garcia |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 17/08684-7 - Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials |
| Grantee: | Célia Regina da Silva Garcia |
| Support Opportunities: | Research Projects - Thematic Grants |