Blocking IP3 signal transduction pathways inhibits melatonin-induced Ca2+ signals and impairs P. falciparum development and proliferation in erythrocytes

Cell Calcium
Mateus Fila PeceninCélia R S Garcia

Abstract

Inositol 1,4,5 trisphosphate (IP3) signaling plays a crucial role in a wide range of eukaryotic processes. In Plasmodium falciparum, IP3 elicits Ca2+ release from intracellular Ca2+ stores, even though no IP3 receptor homolog has been identified to date. The human host hormone melatonin plays a key role in entraining the P. falciparum life cycle in the intraerythrocytic stages, apparently through an IP3-dependent Ca2+ signal. The melatonin-induced cytosolic Ca2+ ([Ca2+]cyt) increase and malaria cell cycle can be blocked by the IP3 receptor blocker 2-aminoethyl diphenylborinate (2-APB). However, 2-APB also inhibits store-operated Ca2+ entry (SOCE). Therefore, we have used two novel 2-APB derivatives, DPB162-AE and DPB163-AE, which are 100-fold more potent than 2-APB in blocking SOCE in mammalian cells, and appear to act by interfering with clustering of STIM proteins. In the present work we report that DPB162-AE and DPB163-AE block the [Ca2+]cyt rise in response to melatonin in P. falciparum, but only at high concentrations. These compounds also block SOCE in the parasite at similarly high concentrations suggesting that P. falciparum SOCE is not activated in the same way as in mammalian cells. We further find that DPB162-AE and ...Continue Reading

Citations

Oct 28, 2019·Current Molecular Pharmacology·Melvin N RosalezMarvin A Soriano-Ursúa
Jan 21, 2021·International Journal of Molecular Sciences·Pedro H ScarpelliCelia R S Garcia
Aug 17, 2021·Frontiers in Cellular and Infection Microbiology·Lucas Silva de OliveiraSébastien Charneau

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.