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 journalArticle

19 Citations (Scopus)

Abstract

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
Volume420
Issue number4
DOIs
Publication statusPublished - 2012 Apr 20

Fingerprint

Clusterin
Drosophila melanogaster
Diptera
Aging of materials
Glutamate-Ammonia Ligase
Disulfides
Reactive Oxygen Species
Metals
Biological Phenomena
Oxidation
Ethylmaleimide
Oxidative stress
Hemolymph
Cell Aging
Motor Neurons

Keywords

  • Antioxidant
  • Clusterin
  • Drosophila
  • Lifespan
  • Motoneuron

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster. / Lee, Young Nam; Shim, Young Jun; Kang, Byeong Ho; Park, Joong Jean; Min, Bon Hong.

In: Biochemical and Biophysical Research Communications, Vol. 420, No. 4, 20.04.2012, p. 851-856.

Research output: Contribution to journalArticle

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