Role of metallothioneins in superoxide radical generation during copper redox cycling: defining the fundamental function of metallothioneins.
In order to demonstrate the in vivo antioxidant properties of metallothioneins (MTs), the bacteria Escherichia coli was used as a cell reactor in which we compared the metal binding and antioxidative functions of MTs from different species, with different structures and polypeptide lengths. No protective effects of cytoplasmic MTs from cadmium (Cd) or zinc (Zn) contamination were observed in a wild-type E. coli strain, although these MTs can efficiently bind both Cd and Zn. To test their antioxidant properties, MTs were expressed within the cytoplasm of a sodA sodB deficient mutated strain (QC1726). However, a paradoxical MT toxicity was found when this strain was contaminated with Cd and Zn, suggesting that in a wild-type strain, superoxide dismutase counteracts MT toxicity. The most toxic MT was the one with the strongest Cd and Zn binding capacities. This toxic effect was linked to the generation of superoxide radicals, since a Cd-contaminated QC1726 strain expressing oyster MT isoforms produced 75-85% more O(2)*(-) than the control QC1726 strain. Conversely, under anaerobiosis or in the presence of a copper chelator, MTs protected QC1726 strain from Cd and Zn contamination. A model is proposed to explain the observed MT toxicity.
Achard-Joris
Maud
M
UMR 5805 CNRS - Université Bordeaux 1, Team Géochimie et Ecotoxicologie des Métaux dans les systèmes Aquatiques, Station Marine d'Arcachon, Place du Dr. Peyneau, 33120 Arcachon, France.
Moreau
Jean-Luc
JL
Lucas
Megumi
M
Baudrimont
Magalie
M
Mesmer-Dudons
Nathalie
N
Gonzalez
Patrice
P
Boudou
Alain
A
Bourdineaud
Jean-Paul
JP
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity; D003300:Copper / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism / Q000648:ultrastructure; D020128:Inhibitory Concentration 50; D008668:Metallothionein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D019216:Metals, Heavy / Q000378:metabolism* / Q000633:toxicity; D008954:Models, Biological; D010084:Oxidation-Reduction; D010957:Plasmids; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism / Q000633:toxicity
D000975:Antioxidants; D019216:Metals, Heavy; D020033:Protein Isoforms; D002104:Cadmium; D013481:Superoxides; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D015032:Zinc