[Metallothioneins: the structure and mechanisms of action]

Metallothioneins (MT)--4 groups (MT-I, II, III and IV) of low molecular mass (approximately 6.5 kDa, 61-62 amino acid residues) cytosol proteins. They are rich in sulphur--20 residues for cysteine, are found in cytosol and nuclei of eucaryotic cells. MT-I and MT-II are found in all animal tissues, MT-III and MT-IV--in the brain. The functions of MT are regulation and control of redox-homeostasis, thioldisulphide equilibrium in the cell in synergism with GSH. MT molecule involve two domains, alpha and beta. MT gene promoter have response elements to metals (MRE), to glucocorticoids (GRE) and to oxidative agents, electrophilic compounds and xenobiotics (ARE). Expression and synthesis of MT are induced for heavy metals (Zn, Cu, Cd and so Hg, Pb, As, Ni, Ag a.o.); glucocorticoids and other stress-hormones and cytokines; free radicals, peroxides, cancerogens and antitumor drugs, UV and ionizing radiation. Zn and partially Cu are physiological inductors of MT. Other inductors act more or less actively as stress-agents. Zinc stabilizes MT molecule, enhances some of their functional activities as a scavenger of metal ions, of free radicals, toxins and xenobiotics. MT are exceptional protection agents for embryo and adult from Cd and other heavy metals, from ionizing radiation, cancerogens, alkylating and DNA-linked agents, from oxidative stress. MT realizes negative control of immune system functions, of transcription factor NF-kB activity. The use of genetic engineering achievements (transgenic mice with defective MTF-1-genes and MT-overexpressing genes) enlarge the possibilities of MT study and application.