Thioredoxin-linked metabolism in Entamoeba histolytica

Arias, Diego Gustavo; Gutierrez, César E.; Iglesias, Alberto A.; Guerrero, Sandra

doi:10.1016/j.freeradbiomed.2007.02.012

Cited by 38 publications

(56 citation statements)

References 39 publications

(68 reference statements)

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“…In reverting the disulphide bridge again to the two cysteine residues, they were active TXN and TRX found in trypanosomatids [18,45,46], as well as TRXs from E. histolytica and L-cysteine, a compound that has been identified as a key redox metabolite in the parasite [33]. Our results give additional relevance to the functionality of the TRX system recently identified as a main component of the redox machinery in the protozoon [16,17]. In such a way, in E. histolytica TRXs could be involved not only in degradation of reactive oxygen species, but mainly participating in mechanisms for regulating the activity of enzymes through posttranslational modification.…”

Section: Discussionsupporting

confidence: 65%

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

et al. 2011

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a b s t r a c tAmoebiasis is an intestinal infection caused by the human pathogen Entamoeba histolytica and representing the third leading cause of death by parasites in the world. Host-parasite interactions mainly involve anchored glycoconjugates localized in the surface of the parasitic cell. In protozoa, synthesis of structural oligo-and polysaccharides occurs via UDP-glucose, generated in a reaction catalyzed by UDPglucose pyrophosphorylase. We report the molecular cloning of the gene coding for this enzyme from genomic DNA of E. histolytica and its recombinant expression in Escherichia coli cells. The purified enzyme was kinetically characterized, catalyzing UDP-glucose synthesis and pyrophosphorolysis with V max values of 95 U/mg and 3 U/mg, respectively, and affinity for substrates comparable to those found for the enzyme from other sources. Enzyme activity was affected by redox modification of thiol groups. Different oxidants, including diamide, hydrogen peroxide and sodium nitroprusside inactivated the enzyme. The process was completely reverted by reducing agents, mainly cysteine, dithiothreitol, and thioredoxin. Characterization of the enzyme mutants C94S, C108S, C191S, C354S, C378S, C108/378S, M106S and M106C supported a molecular mechanism for the redox regulation. Molecular modeling confirmed the role of specific cysteine and methionine residues as targets for redox modification in the entamoebic enzyme. Our results suggest that UDP-glucose pyrophosphorylase is a regulated enzyme in E. histolytica. Interestingly, results strongly agree with the occurrence of a physiological redox mechanism modulating enzyme activity, which would critically affect carbohydrate metabolism in the protozoon.

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Section: Discussionsupporting

confidence: 65%

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

et al. 2011

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“…In contrast to this notion, however, we could not observe any reduction of Prx 1 by TrxR in an in vitro enzyme assay. Finally, it is interesting to note that the spatial organization of TrxR in E. histolytica is different where it distinctly localizes to nodules beneath the cytoplasmic membrane (Arias et al 2007), suggesting a different role for the enzyme in E. histolytica as compared with G. lamblia.…”

Section: Xaa-pro Dipeptidase Gl50803_17327mentioning

confidence: 99%

“…It has a microaerophilic/anaerobic lifestyle which renders it vulnerable to oxygen and reactive oxygen species (Gillin and Diamond, 1981;Lloyd et al 2000;Paget et al 2004). Like other microaerophilic protist parasites, such as Trichomonas vaginalis (Coombs et al 2004) and Entamoeba histolytica (Arias et al 2007), G. lamblia possesses antioxidant enzyme pathways for the defence against oxidative stress (Mastronicola et al 2014(Mastronicola et al , 2016. It is well established that the thioredoxin-mediated redox system, comprising thioredoxin reductase (TrxR), the electron shuttle protein thioredoxin, and peroxiredoxins (Lu and Holmgren, 2014), plays a central role in the antioxidant defence.…”

Section: Introductionmentioning

confidence: 99%

Giardia lamblia: missing evidence for a canonical thioredoxin system

et al. 2017

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The microaerophilic protozoan parasite Giardia lamblia occurs globally and causes dysentery in humans and animals. Since it is very sensitive to oxygen and reactive oxygen species, G. lamblia disposes over several enzymatic pathways to counter oxidative stress. One of the enzymes involved is thioredoxin reductase (TrxR), a central redox regulator that indirectly reduces peroxiredoxins via thioredoxin, an electron shuttle protein. Interestingly, the components of the TrxR-mediated redox system, including functional thioredoxins, have so far not been described despite their surmised importance for parasite survival. We aimed at filling this gap and attempted to identify functional thioredoxins and other interaction partners of TrxR in G. lamblia. To this end, we conducted database searches and expressed three recombinant candidate thioredoxins in Escherichia coli for ensuing enzyme assays. Further, coimmunoprecipitation experiments were conducted in order to identify further components of the thioredoxin redox network. Finally, the cellular localization of TrxR and peroxiredoxin 1 was determined by immunofluorescence microscopy. Surprisingly, our endeavours did not result in the identification of a functional thioredoxin or other credible interaction partners of TrxR. We, therefore, conclude that there is currently no evidence for a canonical thioredoxin redox network in G. lamblia.

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“…For virulence factor of this organism is considered its ability to deal with the increased oxidative stress and with high concentration of reactive oxygen metabolites (Akbar et al 2004). The main redox system is Trx system with peroxiredoxin and cofactor NADPH, which can successfully reduce hydroperoxides (Arias et al 2007).…”

Section: Thioredoxin System Of Selected Pathogens As a Therapeutic Tamentioning

confidence: 99%

Thioredoxin system – a novel therapeutic target

Koháryová¹,

Kollárová²

2015

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Abstract. Nowadays there are numerous pathogens that have created a resistance to commonly used antibiotics and drugs. Therefore research is focused on finding new therapeutic targets and on determination of their 3D structures that could help in designing new effective substances and inhibitors. Thioredoxin system not only plays a crucial role as thiol/disulfide redox controller, it is also essential for certain organisms as the only system ensuring the redox homeostasis. It is the redox-regulating function, which makes thioredoxin and thioredoxin reductase attractive for scientific research, especially in many studies of diseases caused by redox instability. Thanks to these facts, the proteins of thioredoxin system are suitable candidates for new therapeutic purposes. In this review we summarized the basic features of the thioredoxin system, we justified why the proteins of thioredoxin system are appropriate therapeutical targets and we provided overview of the possibilities of their inhibition by several types of inhibitors.

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Thioredoxin-linked metabolism in Entamoeba histolytica

Cited by 38 publications

References 39 publications

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

Giardia lamblia: missing evidence for a canonical thioredoxin system

Thioredoxin system – a novel therapeutic target

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