JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span

Cited 104 time in scopus
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Title
JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span
Author(s)
Kyu-Sun Lee; K Lijima-Ando; K Lijima; W J Lee; J H Lee; Kweon Yu; D S Lee
Bibliographic Citation
Journal of Biological Chemistry, vol. 284, no. 43, pp. 29454-29461
Publication Year
2009
Abstract
Activation of c-Jun N-terminal kinase (JNK) signaling in neurons increases stress resistance and extends life span, in part through FOXO-mediated transcription in Drosophila. However, the JNK/FOXO target genes are unknown. Here, we identified Jafrac1, a Drosophila homolog of human Peroxiredoxin II (hPrxII), as a downstream effecter of JNK/FOXO signaling in neurons that enhances stress resistance and extends life span. We found that Jafrac1 was expressed in the adult brain and induced by paraquat, a reactive oxygen species-generating chemical.RNA interference-mediated neuronal knockdown of Jafrac1 enhanced, while neuronal overexpression of Jafrac1 and hPrxII suppressed, paraquat-induced lethality in flies. Neuronal expression of Jafrac1 also significantly reduced ROS levels, restored mitochondrial function, and attenuated JNK activation caused by paraquat. Activation of JNK/FOXO signaling in neurons increased the Jafrac1 expression level under both normal and oxidative stressed conditions. Moreover, neuronal knockdown of Jafrac1 shortened, while overexpression of Jafrac1 and hPrxII extended, the life span in flies. These results support the hypothesis that JNK/FOXO signaling extends life span via amelioration of oxidative damage and mitochondrial dysfunction in neurons.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M109.028027
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > 1. Journal Articles
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