Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum

Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum

Author Budu, Alexandre Autor UNIFESP Google Scholar
Gomes, Mayrim M. Autor UNIFESP Google Scholar
Melo, Pollyana M. Autor UNIFESP Google Scholar
Maluf, Sarah El Chamy Autor UNIFESP Google Scholar
Bagnaresi, Piero Autor UNIFESP Google Scholar
Azevedo, Mauro F. Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Gazarini, Marcos L. Autor UNIFESP Google Scholar
Abstract Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca2+-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca2+](cyt)) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca2+-free conditions, the [Ca2+](cyt) rise elicited by CZ treatment was similar to 3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca2+/H+ ionophore ionomycin (ION) and the Na+/H+ ionophore monensin (MON) suggest that the [Ca2+](cyt)-increasing effect of CZ is driven by the removal of Ca2+ from at least one Ca2+-CaM-related (CaMR) protein as well as by the mobilization of Ca2+ from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca2+ elicited by CZ. Finally, the modulation of membrane Ca2+ channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co2+ but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca2+ channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca2+ reservoir in the parasite. (C) 2015 Elsevier Inc. All rights reserved.
Keywords Calcium signaling
Calmodulin
Plasmodium falciparum
Calcium channels
Malaria
Calmidazolium
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor FAPESP
CNPq
Grant number FAPESP: 09/54598-9
FAPESP: 13/12913-0
FAPESP: 11/14403-4
FAPESP: 2015/07182-2
CNPq: 482400/2013-7
CNPq: 473.226/2010-3
CNPq: 141919/2014-0
Date 2016
Published in Cellular Signalling. New York, v. 28, n. 3, p. 125-135, 2016.
ISSN 0898-6568 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Inc
Extent 125-135
Origin http://dx.doi.org/10.1016/j.cellsig.2015.12.003
Access rights Closed access
Type Article
Web of Science ID WOS:000369458000003
URI https://repositorio.unifesp.br/handle/11600/57945

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