Different redox states of metallothionein/thionein in biological tissue.
Mammalian metallothioneins are redox-active metalloproteins. In the case of zinc metallothioneins, the redox activity resides in the cysteine sulfur ligands of zinc. Oxidation releases zinc, whereas reduction re-generates zinc-binding capacity. Attempts to demonstrate the presence of the apoprotein (thionein) and the oxidized protein (thionin) in tissues posed tremendous analytical challenges. One emerging strategy is differential chemical modification of cysteine residues in the protein. Chemical modification distinguishes three states of the cysteine ligands (reduced, oxidized and metal-bound) based on (i) quenched reactivity of the thiolates when bound to metal ions and restoration of thiol reactivity in the presence of metal-ion-chelating agents, and (ii) modification of free thiols with alkylating agents and subsequent reduction of disulfides to yield reactive thiols. Under normal physiological conditions, metallothionein exists in three states in rat liver and in cell lines. Ras-mediated oncogenic transformation of normal HOSE (human ovarian surface epithelial) cells induces oxidative stress and increases the amount of thionin and the availability of cellular zinc. These experiments support the notion that metallothionein is a dynamic protein in terms of its redox state and metal content and functions at a juncture of redox and zinc metabolism. Thus redox control of zinc availability from this protein establishes multiple methods of zinc-dependent cellular regulation, while the presence of both oxidized and reduced states of the apoprotein suggest that they serve as a redox couple, the generation of which is controlled by metal ion release from metallothionein.
Krezel
Artur
A
Department of Preventive Medicine & Community Health, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Maret
Wolfgang
W
D000818:Animals; D002138:Calibration; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004880:Ergothioneine / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008668:Metallothionein / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D010053:Ovary / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D015398:Signal Transduction; D017186:Titrimetry
D004220:Disulfides; D008670:Metals; D008668:Metallothionein; D004880:Ergothioneine