title: C. elegans metallothioneins: response to and defence against ROS toxicity.
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.
authors.affiliation: King's College London, School of Biomedical Sciences, Pharmaceutical Science Division, London, UK.
authors.forename: Sukaina
authors.initials: S
authors.lastname: Zeitoun-Ghandour
authors.forename: Oksana I
authors.initials: OI
authors.lastname: Leszczyszyn
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Blindauer
authors.forename: Florian M
authors.initials: FM
authors.lastname: Geier
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Bundy
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Stürzenbaum
mesh_terms: D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D004531:Eggs; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D055432:Metabolomics; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000502:physiology*; D010269:Paraquat / Q000633:toxicity; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species; D008668:Metallothionein; D006861:Hydrogen Peroxide; D010269:Paraquat