Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster
Language: 
English
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 (~60 kDa) 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.

Author(s): 
Lee, Young-Nam
Shim, Young-Jun
Kang, Byeong-Ho
Park, Joong-Jean
Min, Bon-Hong
Item Type: 
Journal Article
Publication Title: 
Biochemical and Biophysical Research Communications
Journal Abbreviation: 
Biochem. Biophys. Res. Commun.
Publication Date: 
4/20/2012
Publication Year: 
2012
Pages: 
851-856
Volume: 
420
Issue: 
4
ISSN: 
1090-2104
DOI: 
10.1016/j.bbrc.2012.03.087
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22465014

Turabian/Chicago Citation

Young-Nam Lee, Young-Jun Shim, Byeong-Ho Kang, Joong-Jean Park and Bon-Hong Min. 4/20/2012. "Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster." Biochemical and Biophysical Research Communications 420: 4: 851-856. 10.1016/j.bbrc.2012.03.087.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.bbrc.2012.03.087 | issn = 1090-2104 | volume = 420 | pages = 851-856 | last = Lee | first = Young-Nam | coauthors = Shim, Young-Jun, Kang, Byeong-Ho, Park, Joong-Jean, Min, Bon-Hong | title = Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster | journal = Biochemical and Biophysical Research Communications | date = 4/20/2012 | pmid = | pmc = }} </ref>