Signaling transcript profile of the asexual intraerythrocytic development cycle of Plasmodium falciparum induced by melatonin and cAMP
Wânia Rezende Lima1,6,*, Giulliana Tessarin-Almeida1,*, Andrei Rozanski2, Kleber S. Parreira3, Miriam S. Moraes1, David C. Martins4, Ronaldo F. Hashimoto5, Pedro A.F. Galante2 and Célia R.S. Garcia1
1 Departamento de Fisiologia, Instituto de Biociências, Universidade de Sao Paulo, Sao Paulo, Brazil
2 Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil
3 Departamento de Imunologia e Parasitologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Brazil
4 Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Paulo, Brazil
5 Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, Brazil
6 Instituto de Ciências Exatas e Naturais (ICEN)- Medicina, Universidade Federal do Mato Grosso - Campus Rondonópolis, Brazil
* These first authors equally contributed to this work
Correspondence:
Célia R.S. Garcia, email:
Keywords: transcripts, malaria, P. falciparum, melatonin, cAMP, ubiquitin proteasome
Received: May 31, 2016 Accepted: September 25, 2016 Published: October 03, 2016
Abstract
According to the World Health Organization (WHO), Plasmodium falciparum is the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP. Therefore, we performed RNA sequencing (RNA-Seq) analysis in P. falciparum erythrocytic stages (ring, trophozoite and schizont) treated with MEL and cAMP. To investigate the expression profile of P. falciparum genes regulated by MEL and cAMP, we performed RNA-Seq analysis in three P. falciparum strains (control, 3D7; protein kinase 7 knockout, PfPK7-; and PfPK7 complement, PfPK7C). In the 3D7 strain, 38 genes were differentially expressed upon MEL treatment; however,none of the genes in the trophozoite (T) stagePfPK7- knockout parasites were differentially expressed upon MEL treatment for 5 hours compared to untreated controls, suggesting that PfPK7 may be involved in the signaling leading to differential gene expression. Moreover, we found that MEL modified the mRNA expression of genes encoding membrane proteins, zinc ion-binding proteins and nucleic acid-binding proteins, which might influence numerous functions in the parasite. The RNA-Seq data following treatment with cAMP show that this molecule modulates different genes throughout the intraerythrocytic cycle, namely, 75, 101 and 141 genes, respectively, in the ring (R), T and schizont (S) stages. Our results highlight P. falciparum’sperception of the external milieu through the signaling molecules MEL and cAMP, which are able to drive to changes in gene expression in the parasite.
