Stress response and cytoskeletal proteins involved in erythrocyte membrane remodeling upon Plasmodium falciparum invasion are differentially carbonylated in G6PD A− deficiency

Méndez, Darío; Linares, María; Díez, Amalia; Puyet, Antonio; Bautista, José M.

doi:10.1016/j.freeradbiomed.2011.02.024

Cited by 27 publications

(27 citation statements)

References 48 publications

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“…This major CA isoenzymes in the RBCs can provide the G6PD deficient person with some extent of protection against oxidative damage [43]. Consequently, an increase in oxidative damage occurrence to the RBC membranes contributes to phosphatidylserine externalization, the accelerated senescence, either directly through oxidation of thiol groups or indirectly by the binding of hemoglobin denaturation products (hemichromes and Heinz bodies) [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Changes in red blood cell membrane structure in G6PD deficiency: An atomic force microscopy study

Tang

Jiang

Xiao

et al. 2015

Clinica Chimica Acta

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Section: Discussionmentioning

confidence: 99%

Changes in red blood cell membrane structure in G6PD deficiency: An atomic force microscopy study

Tang

Jiang

Xiao

et al. 2015

Clinica Chimica Acta

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“…Two gene products required for the function of the non-OxPPP, transaldolase and NAD + kinase, could not be detected in a bioinformatic analysis of completed Plasmodium genomes [17]. However, the ability to label P. falciparum nucleic acids with cells fed [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C-glucose suggests that this non-oxidative arm is intact, because the 1-C position of glucose would not be incorporated into ribose 5-phosphate synthesised via the oxidative arm [19].…”

Section: Pfglupho Is a Target Of The Antimalarial Compound Ellagic Acidmentioning

confidence: 99%

Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target

et al. 2015

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The malarial parasite Plasmodium falciparum is exposed to substantial redox challenges during its complex life cycle. In intraerythrocytic parasites, haemoglobin breakdown is a major source of reactive oxygen species. Deficiencies in human glucose‐6‐phosphate dehydrogenase, the initial enzyme in the pentose phosphate pathway (PPP), lead to a disturbed redox equilibrium in infected erythrocytes and partial protection against severe malaria. In P. falciparum, the first two reactions of the PPP are catalysed by the bifunctional enzyme glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase (PfGluPho). This enzyme differs structurally from its human counterparts and represents a potential target for drugs. In the present study we used epitope tagging of endogenous PfGluPho to verify that the enzyme localises to the parasite cytosol. Furthermore, attempted double crossover disruption of the PfGluPho gene indicates that the enzyme is essential for the growth of blood stage parasites. As a further step towards targeting PfGluPho pharmacologically, ellagic acid was characterised as a potent PfGluPho inhibitor with an IC50 of 76 nm. Interestingly, pro‐oxidative drugs or treatment of the parasites with H2O2 only slightly altered PfGluPho expression or activity under the conditions tested. Furthermore, metabolic profiling suggested that pro‐oxidative drugs do not significantly perturb the abundance of PPP intermediates. These data indicate that PfGluPho is essential in asexual parasites, but that the oxidative arm of the PPP is not strongly regulated in response to oxidative challenge.

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“…Pantaleo et al suggested that phosphorylation of tyrosine residues in band 3 is involved in band 3 clustering (29). Furthermore, it was shown recently that malaria infections cause selective oxidation of proteins in the host cell, including membrane, oxidative stress defense, and stress response proteins (30). Additionally, cellmediated immune activity may be involved in G6PD deficiency-related malaria protection (31).…”

Section: G6pd Deficiencymentioning

confidence: 99%

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

2012

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Malaria is still one of the most threatening diseases worldwide. The high drug resistance rates of malarial parasites make its eradication difficult and furthermore necessitate the development of new antimalarial drugs. Plasmodium falciparum is responsible for severe malaria and therefore of special interest with regard to drug development. Plasmodium parasites are highly dependent on glucose and very sensitive to oxidative stress; two observations that drew interest to the pentose phosphate pathway (PPP) with its key enzyme glucose‐6‐phosphate dehydrogenase (G6PD). A central position of the PPP for malaria parasites is supported by the fact that human G6PD deficiency protects to a certain degree from malaria infections. Plasmodium parasites and the human host possess a complete PPP, both of which seem to be important for the parasites. Interestingly, there are major differences between parasite and human G6PD, making the enzyme of Plasmodium a promising target for antimalarial drug design. This review gives an overview of the current state of research on glucose‐6‐phosphate metabolism in P. falciparum and its impact on malaria infections. Moreover, the unique characteristics of the enzyme G6PD in P. falciparum are discussed, upon which its current status as promising target for drug development is based. © 2012 IUBMB IUBMB Life, 64(7): 603–611, 2012

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Stress response and cytoskeletal proteins involved in erythrocyte membrane remodeling upon Plasmodium falciparum invasion are differentially carbonylated in G6PD A− deficiency

Cited by 27 publications

References 48 publications

Changes in red blood cell membrane structure in G6PD deficiency: An atomic force microscopy study

Changes in red blood cell membrane structure in G6PD deficiency: An atomic force microscopy study

Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

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