Chemistry and biology of mammalian metallothioneins

Abstract

Metallothioneins (MTs) are a class of ubiquitously occurring low molecular mass, cysteine- and metal-rich proteins containing sulfur-based metal clusters formed with Zn(II), Cd(II), and Cu(I) ions. In mammals, four distinct MT isoforms designated MT-1 through MT-4 exist. The first discovered MT-1/MT-2 are widely expressed isoforms, whose biosynthesis is inducible by a wide range of stimuli, including metals, drugs, and inflammatory mediators. In contrast, MT-3 and MT-4 are noninducible proteins, with their expression primarily confined to the central nervous system and certain squamous epithelia, respectively. MT-1 through MT-3 have been reported to be secreted, suggesting that they may play different biological roles in the intracellular and extracellular space. Recent reports established that these isoforms play an important protective role in brain injury and metal-linked neurodegenerative diseases. In the postgenomic era, it is becoming increasingly clear that MTs fulfill multiple functions, including the involvement in zinc and copper homeostasis, protection against heavy metal toxicity, and oxidative damage. All mammalian MTs are monomeric proteins, containing two metal-thiolate clusters. In this review, after a brief summary of the historical milestones of the MT-1/MT-2 research, the recent advances in the structure, chemistry, and biological function of MT-3 and MT-4 are discussed.

Metallothionein differentially affects the host response to Listeria infection both with and without an additional stress from cold-restraint

“…In addition to the MT level affecting the redox status of cells (Maret 2011;Vašák and Meloni 2011;Torreggiani et al 2013), MT may be affecting cation levels, including Ca 2+ , which directly and indirectly can affect oxidative and ER stress (Dai et al 2012;Hu et al 2013) as well as immunity.…”

Changes in Metallothionein Isoform Expression in the Bones of Ovariectomized Rats

“…Metallothionein (MT) is a low-molecular-weight and metalbinding protein that was purified from horse kidneys by Vallee et al in 1957 as a protein that contained abundant metal and sulfur 1) .…”

Cloning, characterization, and expression of cadmium-induced metallothionein-2 gene from earthworm Pheretima aspergillum (E. Perrier)

“…In fact, MTs are unusually rich in cysteine residues that coordinate multiple metal ions under physiological conditions (Palmiter, 1998). Multiple isoforms have been reported in many mammals (Vašák and Meloni, 2011) and invertebrates (Hockner et al, 2011), and recent progress in molecular biology allows a more precise characterization of these different forms. In some invertebrates such as Lumbricus rubellus, two MT isoforms have been identified and cloned.…”