The PfNF-YB transcription factor is a downstream target of melatonin and cAMP signalling in the human malaria parasite Plasmodium falciparum.
Plasmodium falciparum causes the most severe form of malaria and is responsible for the majority of deaths worldwide. The mechanism of cell cycle control within intra-erythrocytic stages has been examined as a potential means of a promising way to identifying how to stop parasite development in red blood cells. Our group determined that melatonin increases parasitemia in P. falciparum and P. chabaudi through a complex signalling cascade. In vertebrates, melatonin controls the expression of transcription factors, leading us to postulate rather that the indoleamine would affect PfNF-YB expression in human malaria parasites. We show here that PfNF-YB transcription factor is highly expressed and colocalized in the nucleus in mature parasites during intra-erythrocytic stages, thus suggesting an important role in cell division. Moreover, we demonstrate for the first time that melatonin and cAMP modulate the PfNF-YB transcription factor expression in P. falciparum at erythrocytic stages. In addition, PfNF-YB is found to be more ubiquitinated in the presence of melatonin. Finally, the proteasome inhibitor bortezomib is able to modulate PfNF-YB expression as well. Taken together, our dada reinforce the role played by melatonin in the cell cycle control of P. falciparum and point this indolamine as a target to develop new antimalarial drugs.
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Wânia R
WR
Lima
Miriam
M
Moraes
Eduardo
E
Alves
Mauro F
MF
Azevedo
Dario O
DO
Passos
Célia R S
CR
Garcia
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D000242:Cyclic AMP / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008550:Melatonin / Q000378:metabolism*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D000962:Antimalarials; D014157:Transcription Factors; D000242:Cyclic AMP; D008550:Melatonin