History of Biomarkers - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 22

2.3.5 Metallothioneins
MTs are nonenzymatic proteins with a low molecular weight (12-15 kDa), high cysteine
content, heat stability, and no aromatic amino acids. The thiol groups (-SH) of cysteine res-
idues enable MTs to bind particular trace metals. The first MT was found in equine renal
cortex (Margoshes and Vallee 1957). MTs or MT-like proteins have since been reported in
many vertebrates including many species of fish (reviewed by Hamilton and Mehrle 1986),
and in aquatic invertebrates (reviewed by Amiard et al. 2006) such as echinoderms (Riek
et al. 1999), mollusks (Amiard-Triquet et al. 1998; Bebianno and Langston 1998; Bebianno et
al. 2003) and their larvae (Damiens et al. 2004), and crustaceans (Roesijadi 1992), but also
in terrestrial invertebrates (Dallinger 1996). In aquatic species, MT concentrations were
measured mainly in tissues involved in the uptake, storage, and excretion of metals such
as gills, digestive glands, and kidneys, but also in muscular and nervous tissues. Fowler et
al. (1987) defined three classes of MT according to the location of cysteine residues in the
amino acid sequences. Class I includes MTs of vertebrates and MTs with a closely similar
structure (mollusks, crustaceans). Class II includes MTs whose structure does not resem-
ble that of class I ( Drosophila , sea urchins, nematodes, fungi, cyanobacteria), and finally the
third class includes the nonprotein MTs, synthesized from glutathione such as phytochela-
tins, present in plants.
Several reviews have synthesized the research completed mainly in aquatic species con-
cerning the structure and the functions of MTs as well as the progress of assay techniques
(Roesijadi 1992, 1996; Roméo et al. 1997; Cosson and Amiard 2000; Cosson 2000; Isani et al.
2000; Amiard et al. 2006). MTs whose behavior is related to the chemistry of thiol groups
assume many biological functions and even if some remain under discussion, in gen-
eral, authors agree on the participation of MTs in the homeostasis and detoxification of
essential metals such as zinc and copper and in the detoxification of nonessential metals
such as cadmium and mercury. Studies have also shown MT involvement in protection
mechanisms against oxidative stress, apoptosis, and growth regulation of nervous cells
(Cavaletto et al. 2002).
In vertebrates as well as in invertebrates, MT levels differ according to species and tis-
sues. They are generally higher in the gills and digestive gland in mollusks (Baudrimont
et al. 1997). The concentrations vary in different tissues not only according to the devel-
opmental stage, age, sex, size, and nutritional status of an organism, but also according
to their gonadic development under hormonal control (Hamza-Chaffai et al. 1995, 1999;
Leung and Furness 2001; Bebianno et al. 2003; Riggio et al. 2003; Leiniö and Lehtonen
2005). If the organism is exposed to a very high metal concentration, MT synthesis can be
inhibited, as demonstrated by George et al. (1992).
MT synthesis is mainly induced by metals (essential or not) such as Cu, Zn, Cd, Hg,
and Ag but also to a lesser extent by organic compounds such as some pesticides or anti-
biotics. The great variability of induction and the various abiotic or biotic factors influenc-
ing MT synthesis lead to contradictory results in the literature, which have been discussed
in a review relating to the role of MTs in invertebrates and their use as biomarkers (Amiard
et al. 2006).
For about the past 20 years, many studies carried out in laboratory conditions and in
situ have shown the potential of increased concentrations in MTs for use as biomark-
ers of exposure to contaminant metals. Currently in ecotoxicological studies carried out
in terrestrial and aquatic environments, their measurement may be integrated into a
multibiomarker approach so inter alia mitigating for the presence of other inducers than
metals.