Regulation of the synthesis of brain metallothioneins

Metallothioneins (MTs) area family of low molecular weight proteins characterized by a high cysteine (about 30%) and heavy metal (Zn2+, Cu+) content. In rodents, there are four known MT isoforms, named MT-I to MT-IV. MT-I and MT-II are two widely expressed isoforms, while MT-III and MT-IV (isoforms recently discovered) have a more restricted expression, normally in the brain and in the keratinizing epithelia, respectively. Since all MT isoforms share a substantial homogeneity regarding their heavy metal binding properties, it seems feasible that they could also share physiological functions. However, the different pattern of expression suggest that the different MT isoforms could in addition have specific roles. Indeed, MT-III (or GIF) was initially discovered as a protein with apparent neuromodulatory effects, which were not shared by the normal counterparts MT-I and MT-II. To gain insight on the putative importance of these three MT isoforms in the brain, it is important to characterize their regulation in normal and pathophysiological states. In this review we summarize the major factors known to affect brain MT regulation.