Redox sensor function of metallothioneins.
In summary, the redox conversions of MT cysteines are likely to be the principal mechanisms for regulation of metal binding and release by this protein. Oxidative and/or nitrosative challenges can serve to promote metal ion release from MT to render their delivery to specific target proteins. It is tempting to consider the potential roles of MTs as redox sensors because of their high sensitivity to cysteine modification, as well as their potential to amplify signals by releasing multiple metal ions. In other words, MTs may act early in a biological signaling cascade that triggers metal-dependent biochemical and cellular responses. Alternatively, uncontrolled release of metals by excessive oxidative stress may contribute to metal toxicity. Because oxidative and nitrosative signaling is ubiquitous within cells, the physiological function of MT demands that efficient recycling of modified cysteines be operative. Little is known regarding the potential mechanisms for the regeneration of MT after oxidative/nitrosative modification, but they may involve endogenous dithiols, such as thioredoxin, and pharmacologically relevant dithiols, such as dihydrolipoate.
Fabisiak
James P
JP
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Borisenko
Gregory G
GG
Liu
Shang-Xi
SX
Tyurin
Vladimir A
VA
Pitt
Bruce R
BR
Kagan
Valerian E
VE
D000818:Animals; D002474:Cell-Free System; D003300:Copper / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008668:Metallothionein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013438:Sulfhydryl Compounds / Q000032:analysis; D015032:Zinc / Q000378:metabolism
D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D003300:Copper; D008668:Metallothionein; D006861:Hydrogen Peroxide; D015032:Zinc