4.5 Article

Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila

期刊

BIOCHEMICAL JOURNAL
卷 419, 期 -, 页码 437-445

出版社

PORTLAND PRESS LTD
DOI: 10.1042/BJ20082003

关键词

aging; apoptosis; development; oxidative stress; peroxiredoxin

资金

  1. National Institute on Aging/National Institutes of Health [R01 AG20715]

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Peroxiredoxin 5 is a distinct isoform of the peroxiredoxin gene family. The antioxidative. and anti-apoptotic functions of peroxiredoxin 5 have been extensively demonstrated in cell Culture experiments. In the present paper, we provide the first functional analysis of peroxiredoxin 5 in a multicellular organism, Drosophila melanogaster. Similar to its mammalian, yeast or human couterparts, dPrx5 (Drosophila peroxiredoxin 5) is expressed in several cellular compartments, including the cytosol, nucleus and the mitochondrion. Global overexpression of dPrx5 in flies increased resistance to oxidative stress and extended their life span by up to 30% under normal conditions. The dprx5(-/-) null flies were comparatively more susceptible to oxidative stress, had higher incidence of apoptosis, and it shortened life span. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) analysis revealed that the dprx5(-/-) null mutant had discernible tissue-specific apoptotic patterns, similar to those observed in control flies exposed to paraquat. In addition, apoptosis was particularly notable in oenocytes. During development the dPrx5 levels co-varied with ecdysone pulses, suggesting inter-relationship between ecdystreroids and dPrx5 expression. The importance of dPrx5 for development was further underscored by the embryonic lethal phenotype of progeny derived front the dprx5(-1-) null mutant. Results from the present study suggest that the antioxidant and anti-apoptotic activities of dPrx5 play a critical role in development and aging of the fly.

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