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Título : The Characterization of the Caenorhabditis elegans Mitochondrial Thioredoxin System Uncovers an Unexpected Protective Role of Thioredoxin Reductase 2 in β-Amyloid Peptide Toxicity
Autor : Cacho-Valadez, Briseida, Muñoz-Lobato, Fernando, Pedrajas, José R., Cabello, Juan, Fierro-González, Juan Carlos, Navas, Plácido, Swoboda, Peter, Link, Chris D., Miranda-Vizuete, Antonio
Palabras clave : Mitochondrial thioredoxin system
Caenorhabditis elegans
Thioredoxin 2
Thioredoxin reductase 2
Protein
Oxygen
Apoptotic
Alzheimer's disease
Fecha de publicación : 15-Feb-2012
Editor: Mary Ann Liebert
Citación : Antioxidants and Redox Signalling
Resumen: Aim: Functional in vivo studies on the mitochondrial thioredoxin system are hampered by the embryonic or larval lethal phenotypes displayed by murine or Drosophila knock-out models. Thus, the access to alternative metazoan knock-out models for the mitochondrial thioredoxin system is of critical importance. Results: We report here the characterization of the mitochondrial thioredoxin system of Caenorhabditis elegans that is composed of the genes trx-2 and trxr-2. We demonstrate that the proteins thioredoxin 2 (TRX-2) and thioredoxin reductase 2 (TRXR-2) localize to the mitochondria of several cells and tissues of the nematode and that trx-2 and trxr-2 are upregulated upon induction of the mitochondrial unfolded protein response. Surprisingly, C. elegans trx-2 (lof ) and trxr-2 (null) single and double mutants are viable and display similar growth rates as wild-type controls. Moreover, the lack of the mitochondrial thioredoxin system does not affect longevity, reactive oxygen species production or the apoptotic program. Interestingly, we found a protective role of TRXR-2 in a transgenic nematode model of Alzheimer's disease (AD) that expresses human β-amyloid peptide and causes an age-dependent progressive paralysis. Hence, trxr-2 downregulation enhanced the paralysis phenotype, while a strong decrease of β-amyloid peptide and amyloid deposits occurred when TRXR-2 was overexpressed. Innovation: C. elegans provides the first viable metazoan knock-out model for the mitochondrial thioredoxin system and identifies a novel role of this system in β-amyloid peptide toxicity and AD. Conclusion: The nematode strains characterized in this work make C. elegans an ideal model organism to study the pathophysiology of the mitochondrial thioredoxin system at the level of a complete organism. Antioxid. Redox Signal. 00, 000–000.
Descripción : 48 páginas, 8 figuras. Material suplementario y métodos 19 páginas, 6 figuras, 3 tablas.
Versión del editor: http://dx.doi.org/10.1089/ars.2011.4265
URI : http://hdl.handle.net/10261/47087
ISSN: 1523-0864
DOI: 10.1089/ars.2011.4265
Fecha de embargo: 2013-06-15
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1 - Cacho-Valadez main revised-2.docArtículo337,5 kBMicrosoft WordView/Open
2 - Cacho-Valadez Supplemental revised-2.docMaterial suplementario y método249 kBMicrosoft WordView/Open
Cacho-Valadez SUP FIG1.tifFigura 1- material suplementario2,02 MBTIFFView/Open
Cacho-Valadez SUP FIG2.tifFigura 2 - material suplementario5 MBTIFFView/Open
Cacho-Valadez SUP FIG3.tifFigura 3 - material suplementario11,52 MBTIFFView/Open
Cacho-Valadez SUP FIG4.tifFigura 4 - material suplementario1,65 MBTIFFView/Open
Cacho-Valadez SUP FIG5.tifFigura 5 - material suplementario4,69 MBTIFFView/Open
Cacho-Valadez SUP FIG6.tifFigura 6 - material suplementario2,08 MBTIFFView/Open
Cacho-ValadezFIG1.tifFigura 1 - artículo575,08 kBTIFFView/Open
Cacho-ValadezFIG2.tifFigura 2 - artículo12,86 MBTIFFView/Open
Cacho-ValadezFIG3.tifFigura 3 - artículo11,66 MBTIFFView/Open
Cacho-ValadezFIG4.tifFigura 4 - artículo278,02 kBTIFFView/Open
Cacho-ValadezFIG5.tifFigura 5 - artículo2,26 MBTIFFView/Open
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Cacho-ValadezFIG7.tifFigura 7 - artículo1,66 MBTIFFView/Open
Cacho-ValadezFIG8.tifFigura 8 - artículo7,59 MBTIFFView/Open
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