Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence

Cruz, Laura N.; Craig, Alister G.; Garcia, Célia Regina da Silva

doi:10.1590/s0001-37652012005000036

Cited by 8 publications

(12 citation statements)

References 158 publications

(41 reference statements)

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“…[57] Finally, ATP is involved in endothelial cell inflammation induced following infection with Plasmodium. [58] Like oxidative stress, RBC infection by P. falciparum induces increased permeability of anions and organic osmolytes. Induction of osmolyte permeability in iRBCs involves autocrine purino-receptor signaling, as extracellular ATP does not induce permeability in uninfected or unoxidized RBCs.…”

Section: Role Of New Permeation Pathways -Nppmentioning

confidence: 99%

ATP, an extracellular signaling molecule in red blood cells: A messenger for malaria?

Ramdani¹,

Langsley²

2014

Biomed J

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Adenosine 5' triphosphate (ATP), discovered in 1929 by Karl Lohmannest, is described as an essential energy source for cells. In the biochemistry of all living organisms, ATP hydrolysis provides the energy required for the chemical reactions of metabolism. It is the precursor of a number of essential enzyme cofactors, such as nicotinamide adenine dinucleotide (NAD + ) and coenzyme A [NAD + , flavin adenine dinucleotide (FAD), and is ATP coenzyme A are all formed from ATP] and is the source of the phosphoryl group in most kinase-mediated phosphorylation reactions. Another essential, but less known function is that ATP plays a very important role as an extracellular signaling molecule, allowing cells and tissues to communicate. ATP is converted into cAMP, a major second messenger involved in many cellular processes, by adenylyl cyclase, a membrane-associated enzyme. In this review, we describe the role of ATP as a beneficial extracellular molecule released by healthy red blood cells (RBCs) in response to hypoxia to mediate a vasodilator signal, by oxidatively stressed RBCs, and by Plasmodium falciparum-infected RBCs (iRBCs), and its similarity with released ATP that by the combined action of the ectonucleotidases CD39 and CD73 is converted to adenosine that mediates sickling in sickle cell disease (SCD).

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Section: Role Of New Permeation Pathways -Nppmentioning

confidence: 99%

ATP, an extracellular signaling molecule in red blood cells: A messenger for malaria?

Ramdani¹,

Langsley²

2014

Biomed J

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“…Although this machinery is not thought to exist in Plasmodium parasites, an analogous system may have evolved to detect this important host protein. Signal transduction regulation inside Plasmodium has been shown as a major mechanism to control parasite development [ 15 ]. In the mammalian host, studies have shown that TNF induces extensive alterations in host microvascular endothelium, including morphological re-organization [ 46 ], release of membrane microparticles [ 47 ], production of other pro-inflammatory cytokines, up-regulation of receptors and apoptosis [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, all of these belong to the host responses to parasite infection, whereas there are only limited numbers of studies about signalling events in parasites themselves, despite the existence of an extensive kinase gene family. For example, signal transduction inside Plasmodium has been shown to be a major mechanism to control parasite development [ 15 ] with regulation in P. falciparum by calcium-dependent protein kinase 7 (PfCDPK7) being reported [ 16 ]. PfCDPK1 has been identified as a Ca 2+ -dependent effector that plays a role in microneme secretion during erythrocyte invasion [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

An external sensing system in Plasmodium falciparum-infected erythrocytes

Cruz

Szestak

Laing

et al. 2016

Malar J

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BackgroundA number of experiments have previously indicated that Plasmodium falciparum-infected erythrocytes (pRBC) were able to sense host environment. The basis of this ability to detect external cues is not known but in screening signalling molecules from pRBC using commercial antibodies, a 34 kDa phosphorylated molecule that possesses such ability was identified.MethodsThe pRBC were exposed to different culture conditions and proteins were extracted for 1D or 2D gel electrophoresis followed by Western blot. The localization of 34 kDa protein was examined by biochemical fractionation followed by Western blot. High-resolution mass spectrometric analysis of immune precipitants was used to identify this protein and real-time quantitative reverse transcriptase polymerase chain reaction was used for detecting mRNA expression level.ResultsThe 34 kDa protein was called PfAB4 has immediate responses (dephosphorylation and rapid turnover) to host environmental stimuli such as serum depletion, osmolality change and cytokine addition. PfAB4 is expressed constitutively throughout the erythrocytic lifecycle with dominant expression in trophozoites 30 h post-infection. Tumour necrosis factor (TNF) treatment induced a transient detectable dephosphorylation of PfAB4 in the ItG strain (2 min after addition) and the level of expression and phosphorylation returned to normal within 1–2 h. PfAB4 localized dominantly in pRBC cytoplasm, with a transient shift to the nucleus under TNF stimulation as shown by biochemical fractionation. High-resolution mass spectrometric analysis of immune precipitants of AB4 antibodies revealed a 34 kDa PfAB4 component as a mixture of proliferating cellular nuclear antigen-1 (PCNA1) and exported protein-2 (EXP2), along with a small number of other inconsistently identified peptides. Different parasite strains have different PfAB4 expression levels, but no significant association between mRNA and PfAB4 levels was seen, indicating that the differences may be at the post-transcriptional, presumably phosphorylation, level. A triple serine phosphorylated PCNA1 peptide was identified from the PfAB4 high expression strain only, providing further evidence that the identity of PfAB4 is PCNA1 in P.falciparum.ConclusionA protein element in the human malaria parasite that responds to external cues, including the pro-inflammatory cytokine TNF have been discovered. Treatment results in a transient change in phosphorylation status of the response element, which also migrates from the parasite cytoplasm to the nucleus. The response element has been identified as PfPCNA1. This sensing response could be regulated by a parasite checkpoint system and be analogous to bacterial two-component signal transduction systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1144-6) contains supplementary material, which is available to authorized users.

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“…Thus, these receptors can be exploited as targets so as to design inhibitors of parasite invasion process (68, 69). ATP is also thought to be involved in the host-induced inflammation following the malaria infection (70). …”

Section: Cyclic Nucleotide-based Signaling During Malariamentioning

confidence: 99%

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

et al. 2017

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Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis. This review is intended to bring out the existing knowledge about the functions and components of the major signaling pathways such as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling, serving the various aspects of the parasitic asexual stage and highlighted the Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and molecular events in cytoadhesion, which elicit the host immune response. This discussion will facilitate a look over essential components for parasite survival and disease progression to be implemented in discovery of novel antimalarial drugs and vaccines.

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Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence

Cited by 8 publications

References 158 publications

ATP, an extracellular signaling molecule in red blood cells: A messenger for malaria?

ATP, an extracellular signaling molecule in red blood cells: A messenger for malaria?

An external sensing system in Plasmodium falciparum-infected erythrocytes

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

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