The Plasmodium falciparum Translationally Controlled Tumor Protein Homolog and Its Reaction with the Antimalarial Drug Artemisinin

Bhisutthibhan, Jamaree; Pan, X. Q.; Hossler, Paul A.; Walker, Daniel J.; Yowell, Charles A.; Carlton, Jane M.; Dame, John B.; Meshnick, Steven R.

doi:10.1074/jbc.273.26.16192

Cited by 234 publications

(181 citation statements)

References 24 publications

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“…Other possible targets of artemisinin are specific parasite proteins, although no details have been reported for such artemisinin-protein adducts. Inhibition of the SERCA orthologue PfATP6 and of the cysteine proteases of P. falciparum by artemisinin and its specific reaction with TCTP have been reported, but it is noteworthy that, in all of these cases, the action of the drug was found to be dependent on the presence of haem and/or some unidentified reducing iron species [19,20]. However, a literature review using the ISI Web of Knowledge revealed that carbon-centred radicals are poor protein alkylators [46].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested that the haem-promoted cleavage of the peroxide in artemisinin, leading to the formation of C-radicals which alkylate some proteins of the malaria parasite [18], also contributes to its antimalarial action. Specific reactions of artemisinin with TCTP (translationally controlled tumour protein) [19], inhibition of the SERCA (sarcoplasmic/endoplasmic-reticulum Ca 2+ -ATPase) orthologue (PfATP6) of P. falciparum [20] and inhibition of P. falciparum cysteine proteases have also been proposed to contribute to its drug activity [21]. On the other hand, Hong et al [22] reported that artemisinin forms covalent adducts with haem in artemisinintreated parasite cultures.…”

Section: Introductionmentioning

confidence: 99%

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Reaction of artemisinin with haemoglobin: implications for antimalarial activity

Kannan

Kumar

Sahal

et al. 2005

Biochemical Journal

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Elucidation of the principal targets of the action of the antimalarial drug artemisinin is an ongoing pursuit that is important for understanding the action of this drug and for the development of more potent analogues. We have examined the chemical reaction of Hb with artemisinin. The protein-bound haem in Hb has been found to react with artemisinin much faster than is the case with free haem. It appears that the uptake of Hb and the accumulation of artemisinin into the food vacuole, together with the preferred reactivity of artemisinin with haem in Hb, may make Hb the primary target of artemisinin's antimalarial action. Both monoalkylated (HA) and dialkylated (HAA) haem derivatives of artemisinin have been isolated. These 'haemarts' bind to PfHRP II (Plasmodium falciparum histidine-rich protein II), inhibiting haemozoin formation, and possess a significantly decreased ability to oxidize ascorbic acid. The accelerated formation of HAA from Hb is expected to decrease the ratio of haem to its alkylated derivatives. The haemarts that are generated from 'haemartoglobins' may bring about the death of malaria parasite by a two-pronged effect of stalling the formation of haemozoin by the competitive inhibition of haem binding to its templates and creating a more reducing environment that is not conducive to the formation of haemozoin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reaction of artemisinin with haemoglobin: implications for antimalarial activity

Kannan

Kumar

Sahal

et al. 2005

Biochemical Journal

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“…Artemisinin: Since the early discovery that TCTP of Plasmodium falciparum is a target protein of the antimalarial drug artemisinin (Bhisutthibhan et al 1998), this drug interaction has been studied in more detail (Chae et al 2006). Artemisinin not only displays antimalarial activity but was also found to be a potent anticancer agent in cellular assay (review in Efferth 2005), and screening for potential targets in this context has confirmed that TCTP is indeed a target for this drug (Efferth 2005(Efferth , 2006.…”

Section: Tctp As An Anticancer Targetmentioning

confidence: 99%

“…It was discovered as one of the target proteins for the antimalarial drug artemisinin (Bhisutthibhan et al 1998). This paper demonstrated that TCTP reacts with artemisinin in situ and in vitro in the presence of haemin and that it binds haemin itself.…”

Section: Tctp In Protozoansmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein. TCTP is able to interact with a large number of other proteins and is therefore involved in many core cell biological processes, predominantly in the response to cellular stresses, such as oxidative stress, heat shock, genotoxic stress, imbalance of ion metabolism as well as other conditions. Mechanistically, TCTP acts as an anti-apoptotic protein, and it is involved in DNA-damage repair and in cellular autophagy. Thus, broadly speaking, TCTP can be considered a cytoprotective protein. In addition, TCTP facilitates cell division through stabilising the mitotic spindle and cell growth through modulating growth signalling pathways and through its interaction with the proteosynthetic machinery of the cell. Due to its activities, both as an anti-apoptotic protein and in promoting cell growth and division, TCTP is also essential in the early development of both animals and plants. Apart from its involvement in various biological processes at the cellular level, TCTP can also act as an extracellular protein and as such has been involved in modulating whole-body defence processes, namely in the mammalian immune system. Extracellular TCTP, typically in its dimerised form, is able to induce the release of cytokines and other signalling molecules from various types of immune cells. There are also several examples, where TCTP was shown to be involved in antiviral/antibacterial defence in lower animals. In plants, the protein appears to have a protective effect against phytotoxic stresses, such as flooding, draught, too high or low temperature, salt stress or exposure to heavy metals. The finding for the latter stress condition is corroborated by earlier reports that TCTP levels are considerably up-regulated upon exposure of earthworms to high levels of heavy metals. Given the involvement of TCTP in many biological processes aimed at maintaining cellular or whole-body homeostasis, it is not surprising that dysregulation of TCTP levels may promote a range of disease processes, foremost cancer. Indeed a large body of evidence now supports a role of TCTP in at least the most predominant types of human cancers. Typically, this can be ascribed to both the anti-apoptotic activity of the protein and to its function in promoting cell growth and division. However, TCTP also appears to be involved in the later stages of cancer progression, such ...

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“…La stimulation des cellules endothéliales vasculaires via les récepteurs H1 conduit à l'augmentation de la perméabilité vasculaire (en particulier dans les veinules postcapillaires) [9] et à la libération de NO (nitric oxide) [10]. Par ailleurs, le SYNTHÈSE REVUES TCTP présentant une forte homologie avec le HRF humain a été identifié chez Plasmodium falciparum [22]. Le TCTP de Plasmodium falciparum a pu être mis en évidence dans le plasma de patients infectés et son activité histaminolibératrice sur les basophiles humains a pu être démontrée [23], suggérant que le TCTP de Plasmodium falciparum peut affecter la réponse immunitaire de l'hôte en influant sur les réponses in vivo par sa capacité à libérer l'histamine [23].…”

Section: Propriétés Biologiques De L'histamine Et De Ses Récepteursunclassified

Rôle de l’histamine et des récepteurs histaminiques dans la pathogenèse du paludisme

et al. 2009

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The Plasmodium falciparum Translationally Controlled Tumor Protein Homolog and Its Reaction with the Antimalarial Drug Artemisinin

Cited by 234 publications

References 24 publications

Reaction of artemisinin with haemoglobin: implications for antimalarial activity

Reaction of artemisinin with haemoglobin: implications for antimalarial activity

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Rôle de l’histamine et des récepteurs histaminiques dans la pathogenèse du paludisme

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