Zeitoun-Ghandour, Sukaina, Leszczyszyn, Oksana I., Blindauer, Claudia A., Geier, Florian M., Bundy, Jacob G. and Stürzenbaum, Stephen R.. (2011) C. elegans metallothioneins : response to and defence against ROS toxicity. Molecular BioSystems, Vol.7 (No.8). pp. 2397-2406. ISSN 1742-206X

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Abstract

The genome of the nematode Caenorhabditis elegans encodes for two multifunctional metal binding metallothioneins (MTs), CeMT-1 and CeMT-2. Here we applied qPCR to identify a transcriptional up-regulation following the exposure to free radical generators (ROS) paraquat or hydrogen peroxide, a trend that was confirmed with Pmtl::GFP expressing alleles. The deletion of the MT loci resulted in an elevation of in vivo levels of hydrogen peroxide and exposure to ROS caused a reduction in total egg production, growth and life span in wild type nematodes, effects that were particularly pronounced in the CeMT-2 and double knockout. Moreover, in vitro incubation of recombinant MTs with hydrogen peroxide demonstrated the presence of direct oxidation of the CeMTs, with zinc released from both isoforms and concomitant formation of intra-molecular disulfides. Finally, metabolic profiling (metabolomic) analysis of wild type and MT knockouts in the presence/absence of oxidative stressors, confirmed the overall trend described by the other experiments, and identified 2-aminoadipate as a potential novel small-molecule marker of oxidative stress. In summary, this study highlights that C. elegans metallothioneins scavenge and protect against reactive oxygen species and potentially against oxidative stress, with CeMT-2 being more effective than CeMT-1.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Caenorhabditis elegans, Active oxygen -- Physiological effect, Free radicals (Chemistry) -- Physiological effect, Metallothionein
Journal or Publication Title:	Molecular BioSystems
Publisher:	Royal Society of Chemistry
ISSN:	1742-206X
Official Date:	2011
Volume:	Vol.7
Number:	No.8
Page Range:	pp. 2397-2406
Identification Number:	10.1039/c1mb05114h
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), AXA Direkt (Firm), Altajir Trust
Grant number:	BB/E025099 (BBSRC), BB/E025064 (BBSRC)
URI:	http://wrap.warwick.ac.uk/id/eprint/38709

Data sourced from Thomson Reuters' Web of Knowledge

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