JEB desktop wallpaper calendar 2016

Journal of Experimental Biology partnership with Dryad

A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative stress adaptation in mammals, Caenorhabditis elegans and Drosophila melanogaster
Andrew M. Pickering, Trisha A. Staab, John Tower, Derek Sieburth, Kelvin J. A. Davies

SUMMARY

In mammalian cells, hydrogen peroxide (H2O2)-induced adaptation to oxidative stress is strongly dependent on an Nrf2 transcription factor-mediated increase in the 20S proteasome. Here, we report that both Caenorhabditis elegans nematode worms and Drosophila melanogaster fruit flies are also capable of adapting to oxidative stress with H2O2 pre-treatment. As in mammalian cells, this adaptive response in worms and flies involves an increase in proteolytic activity and increased expression of the 20S proteasome, but not of the 26S proteasome. We also found that the increase in 20S proteasome expression in both worms and flies, as in mammalian cells, is important for the adaptive response, and that it is mediated by the SKN-1 and CNC-C orthologs of the mammalian Nrf2 transcription factor, respectively. These studies demonstrate that stress mechanisms operative in cell culture also apply in disparate intact organisms across a wide biological diversity.

FOOTNOTES

  • Supplementary material available online at http://jeb.biologists.org/cgi/content/full/216/4/543/DC1

  • FUNDING

    This research was supported by the National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS) [grant no. RO1-ES003598; American Recovery and Reinvestment Act (ARRA) Supplement 3RO1-ES 003598-22S2; both to K.J.A.D.], the Department of Health and Human Services [grant no. AG011833 to J.T.] and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) [grant no. NS071085-02 to D.S.S.]. Deposited in PMC for release after 12 months.

  • LIST OF ABBREVIATIONS

    AMC
    7-amino-4-methylcoumarin
    CNC-C
    D. melanogaster cap’n’collar transcription factor (an ortholog of mammalian Nrf2)
    H2O2
    hydrogen peroxide
    Nrf2
    nuclear factor (erythroid-derived 2)-like 2
    PA28αβ
    proteasome activator 28αβ
    PAS-5
    proteasome α-subunit 5
    PAS-7
    proteasome α-subunit 7
    PBS-3
    Proteasome β-subunit 3
    PBS-5
    Proteasome β-subunit 5
    PBS-6
    proteasome β-subunit 6
    RPN-10
    proteasome regulatory particle non-ATPase-like 10
    SKN-1
    C. elegans SKiNhead-1 transcription factor (an ortholog of mammalian Nrf2)
    Suc-LLVY-AMC
    succinylated peptide N-succinyl-leucine-leucine-valine-tyrosine-7-amino-4-methylcoumarin (used as a peptide substrate to measure proteolytic capacity)
  • View Full Text