Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster

Young Nam Lee, Young Jun Shim, Byeong Ho Kang, Joong Jean Park, Bon Hong Min

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)


    Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes. Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging. To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu S) using the Gal4/UAS system. hClu S protein (~60kDa) was detected in both adult homogenates and larval hemolymphs of flies ubiquitously overexpressing hClu S (da-Gal4>UAS-hClu S) and in motoneurons (D42-Gal4>UAS-hClu S). Interestingly, the mean lifespans of these hClu S-overexpressing flies were significantly greater than those of control flies that exhibited no hClu S induction. hClu S-overexpressing flies also showed significantly greater tolerance to heat shock, wet starvation, and oxidative stress. Furthermore, amounts of reactive oxygen species (ROS) in whole bodies were significantly lower in hClu S-overexpressing flies. In addition, clusterin was found to prevent the inactivation of glutamine synthetase (GS) by metal-catalyzed oxidation (MCO) in vitro, and this protection was only supported by thiol-reducing equivalents, such as, DTT or GSH, and not by ascorbate (a non-thiol MCO system). Furthermore, this protection against GS inactivation by clusterin was abolished by reacting clusterin with N-ethylmaleimide, a sulfhydryl group-modifying agent. Taken together, these results suggest that a disulfide-linked form of clusterin functions as an antioxidant protein via its cysteine sulfhydryl groups to reduce ROS levels and delay the organismal aging in fruit flies.

    Original languageEnglish
    Pages (from-to)851-856
    Number of pages6
    JournalBiochemical and biophysical research communications
    Issue number4
    Publication statusPublished - 2012 Apr 20


    • Antioxidant
    • Clusterin
    • Drosophila
    • Lifespan
    • Motoneuron

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology


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