Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle

Author(s)

Beraldo, Flávio H. ^[1] ; Almeida, Fabiana M. ; Silva, Aline M. da ; Garcia, Célia R. S. ^[4]

Affiliation

^[1] Universidade de São Paulo (USP). Instituto de Biociências - Brasil

^[4] Universidade de São Paulo (USP). Instituto de Biociências - Brasil

• Document type: Journal article
• Source: JOURNAL OF CELL BIOLOGY; v. 170, n. 4, p. 551-557, Aug. 2005.
• Field of knowledge: Biological Sciences - Biochemistry

Abstract

The host hormone melatonin increases cytoplasmic Ca2+ concentration and synchronizes Plasmodium cell cycle (Hotta, C.T., M.L. Gazarini, F.H. Beraldo, F.P. Varotti, C. Lopes, R.P. Markus, T. Pozzan, and C.R. Garcia. 2000. Nat. Cell Biol. 2:466-468). Here we show that in Plasmodium falciparum melatonin induces an increase in cyclic AMP (cAMP) levels and cAMP-dependent protein kinase (PKA) activity (40 and 50%, respectively). When red blood cells infected with P. falciparum are treated with cAMP analogue adenosine 3',5'-cyclic monophosphate N6-benzoyl/PKA activator (6-Bz-cAMP) there is an alteration of the parasite cell cycle. This effect appears to depend on activation of PKA (abolished by the PKA inhibitors adenosine 3',5'-cyclic monophosphorothioate/8 Bromo Rp isomer, PKI [cell permeable peptide], and H89). An unexpected cross talk was found to exist between the cAMP and the Ca2+-dependent signaling pathways. The increases in cAMP by melatonin are inhibited by blocker of phospholipase C U73122, and addition of 6-Bz-cAMP increases cytosolic Ca2+ concentration, through PKA activation. These findings suggest that in Plasmodium a highly complex interplay exists between the Ca2+ and cAMP signaling pathways, but also that the control of the parasite cell cycle by melatonin requires the activation of both second messenger controlled pathways. (AU)

• FAPESP's process: 02/06194-7 - Molecular bases of the transduction of the signal of the cell cycle of malaria parasites
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants