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The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions
Author(s) -
Radyuk Svetla.,
Klichko Vladimir I.,
Michalak Katarzyna,
Orr William C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-214106
Subject(s) - microbiology and biotechnology , endoplasmic reticulum , peroxiredoxin , oxidative stress , biology , proinflammatory cytokine , unfolded protein response , homeostasis , cytosol , inflammation , longevity , lipid peroxidation , chemistry , biochemistry , immunology , genetics , peroxidase , enzyme
Peroxiredoxin 4 (Prx4) has been implicated in a wide variety of biological processes, including development, progression of cancer, inflammation, and antioxidant function. The purpose of this study was to provide further insight into its multiple roles at the whole‐animal level, using Drosophila. Reduced expression of dPrx4 (up to 90%) resulted in greater sensitivity to oxidative stress, an elevated H 2 O 2 flux, and increases in lipid peroxidation, but no effect on longevity. Overexpression at low levels (<2‐fold) gave reduced levels of oxidative damage and tended to show an increase in longevity. Flies expressing dPrx4 globally at high levels (>5‐fold) had a dramatically reduced life span (by 20–80%) and increased apoptosis. Analysis of these overexpressors revealed an aberrant redistribution of the dPrx4 protein from the endoplasmic reticulum (ER) to cytosol and hemolymph. In addition to the known proapoptotic effects of the cytosolic form of dPrx4, dPrx4 overexpression triggered an NF‐κB‐mediated proinflammatory response, similar to that observed in cells under ER stress or when microbially challenged. Finally, we provide the first evidence that dPrx4, on secretion into the hemolymph, elicits a JAK/STAT‐mediated response. The effects on fly survival and homeostasis appear to represent a combination of differential effects dictated in large part by dPrx4 subcellular and tissue‐specific localization.—Radyuk, S. N., Klichko, V. I., Michalak, K., Orr, W. C. The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions. FASEB J. 27, 1426–1438 (2013). www.fasebj.org