Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths.

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Título

Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths.

Tema

ENZIMAS
COMPLEJOS
ANIMALES
INMUNOQUIMICA
BIBLIOGRAFIA NACIONAL QUIMICA
2010

Abstract

The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, in detoxification, Fe/S biogenesis and participate in a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm) parasites studied so far, lack conventional thioredoxin and glutathione systems. Instead, they possess a linked thioredoxin-glutathione system with the selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR) as the single redox hub that controls the overall redox homeostasis. TGR has been recently validated as a drug target for schistosomiasis and new drug leads targeting TGR have recently been identified for these platyhelminth infections that affect more than 200 million people and for which a single drug is currently available. Little is known regarding the genomic structure of flatworm TGRs, the expression of TGR variants and whether the absence of conventional thioredoxin and glutathione systems is a signature of the entire platyhelminth phylum. Results: We examine platyhelminth genomes and transcriptomes and find that all platyhelminth parasites (from classes Cestoda and Trematoda) conform to a biochemical scenario involving, exclusively, a selenium-dependent linked thioredoxin-glutathione system having TGR as a central redox hub. In contrast, the free-living platyhelminth Schmidtea mediterranea (Class Turbellaria) possesses conventional and linked thioredoxin and glutathione systems. We identify TGR variants in Schistosoma spp. derived from a single gene, and demonstrate their expression. We also provide experimental evidence that alternative initiation of transcription and alternative transcript processing contribute to the generation of TGR variants in platyhelminth parasites. Conclusions: Our results indicate that thioredoxin and glutathione pathways differ in parasitic and free-living flatworms and that canonical enzymes were specifically lost in the parasitic lineage. Platyhelminth parasites possess a unique and simplified redox system for diverse essential processes, and thus TGR is an excellent drug target for platyhelminth infections. Inhibition of the central redox wire hub would lead to overall disruption of redox homeostasis and disable DNA synthesis.

Autor

Otero Larre Borges, Lucía
Bonilla, Mariana
Protasio Palomino, Anna Victoria
Gladyshev, Vadim N

Fuente

BMC Genomics v. 11, no.1 art. 237, 2010. -- p. 1-13

Editor

BioMed Central

Fecha

2010

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PDF

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Inglés

Tipo

Artículo

Identificador

doi:10.1186/1471-2164-11-237

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Original Format

PDF
Fecha de agregación
December 16, 2014
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Otero Larre Borges, Lucía, “Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths.,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed October 22, 2020, http://riquim.fq.edu.uy/items/show/2318.
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