Metallothionein: the multipurpose protein

Abstract

Metallothioneins (MTs) are intracellular, low molecular, low molecular weight, cysteine-rich proteins. Ubiquitous in eukaryotes, MTs have unique structural characteristics to give potent metal-binding and redox capabilities. A primary role has not been identified, and remains elusive, as further functions continue to be discovered. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs and inflammatory mediators. In teh gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration and/or redox control. Use of mice with altered gene expression has enhance our understanding of the multifaceted role of MT, emphasised in this review.

Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells

“…45 These Cu and Zn-binding proteins are strictly involved in Zn homeostasis and have been related to Zn absorption. 46 Here, we did not find metallothionein over-expression in IB3-1 cells. However, the up-regulation of metallothioneins in response to increased oxidative stress 30 could be related to the observed increases of intracellular Zn and Cu.…”

Copper induces Cu-ATPase ATP7A mRNA in a fish cell line, SAF1

“…MT induction is known to be transcriptionally regulated by different stimuli including metals, glucocorticoids and oxidative stress (Coyle et al, 2002). The zinc finger metal transcription factor-1 (MTF1) modulates MT induction by binding to specific cis-acting promoter elements (Andrews 2000; Bury et al, 2008).…”

Overexpression of Nelumbo nucifera metallothioneins 2a and 3 enhances seed germination vigor in Arabidopsis

“…Plant MTs are 20 further subdivided into several types (type 1, 2, 3 and 4) according to the distribution of Cys residues (Cobbett et al 2002). In animals, MTs are i nvolved in metal 5 homeostasis and scavenging of reactive oxygen species (Thornalley & Vasak 1985;Palmiter 1998;Suhy et al 1999;Coyle et al 2002). It is also worth noting that many studies have demonstrated that there is a tight correlation between the expression of MT genes and many important physiological processes, such as aging (Yang et al 2006) and cell apoptosis (Raymond et al 2010).…”