The effect of zinc and the role of p53 in copper-induced cellular stress responses.

Metals can directly or indirectly cause an increase in reactive oxygen species (ROS) accumulation in cells, and this may result in programmed cell death. A number of previous studies have shown that zinc (Zn) modulates mitogenic activity via several signalling pathways, such as AKT, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF -κB), AP-1 and p53. The exact role that Zn plays in the regulation of apoptosis remains ambiguous.

Functional characterization of the 5'-upstream region of MTT5 metallothionein gene from Tetrahymena thermophila.

Metallothioneins are ubiquitous small, cysteine-rich, metal-binding proteins that play important roles in intracellular metal homeostasis and detoxification. Very few data are available on the promoter region and the mechanism of metallothionein transcription in Protozoa. In this study, we focused on Tetrahymena thermophila MTT5 5'-flanking region.

The influence of metallothionein on exposure to metals: an in vitro study on cellular models.

In the present study, the interactions between zinc (Zn) and copper (Cu) or iron (Fe) have been examined. Rat hepatoma cell line H4-II-E-C3, fibroblast cell line mutant MT-/-, and wild-type MT+/+ cells treated with ZnSO4 or CuSO4 or FeSO4 or CuSO4+ZnSO4 or ZnSO4+FeSO4 for different times have been employed to study the effect of metallothionein (MT), glutathione (GSH) and metal (Cu, Fe and Zn) accumulation during cellular adaptation to supraphysiological metal concentrations. To investigate the different biological functions in the processes of metal homeostasis and detoxification, the levels of both MT-1 and MT-2 mRNAs have been evaluated.

MTT2, a copper-inducible metallothionein gene from Tetrahymena thermophila.

Metallothioneins (MTs) are ubiquitous, cysteine-rich, metal-binding proteins whose transcriptional activation is induced by a variety of stimuli, in particular heavy metals such as cadmium, copper and zinc. Here we describe the sequence and organization of a novel copper-inducible metallothionein gene (MTT2) from Tetrahymena thermophila. Based on its deduced sequence, the gene encodes a protein 108 amino acids, containing 29 cysteine residues (30%) arranged in motifs characteristic of vertebrate and invertebrate MTs.

Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects.

Copper, zinc and iron are essential metals for different physiological functions, even though their excess can lead to biological damage. This review provides a background of toxicity related to copper, iron and zinc excess, biological mechanisms of their homeostasis and their respective roles in the apoptotic process. The antioxidant action of metallothionein has been highlighted by summarizing the most important findings that confirm the role of zinc in cellular protection in relation to metallothionein expression and apoptotic processes.

Effect of Zn treatment on wild type and MT-null cell lines in relation to apoptotic and/or necrotic processes and on MT isoform gene expression.

It has been shown in various systems that zinc is able to antagonize the catalytic properties of the redox-active transition metals iron and copper, although the process is still unclear. Probably, the protective effect of Zn against oxidative stress is mainly due to the induction of a scavenger metal binding protein such as metallothionein (MT), rather than a direct action. To support this hypothesis, in this study, the effects of Zn, Cu, Fe, Zn + Cu and Zn + Fe treatments were investigated in a fibroblast cell line corresponding to an SV40-transformed MT-1/-2 mutant (MT-/-), and in wild type (MT+/+), by valuing metal concentrations and apoptotic and/or necrotic processes.