ReviewInhibitory effect of metals on animal and plant glutathione transferases
Introduction
Metal pollutants are one of the greatest challenges to the environment and human health. Metals enter the biosphere by natural processes (e.g. volcanism, weathering) and human activities such as mining, fuel combustion and many other industrial processes [1]. The toxicological relevance of metals depends on their chemical species, i.e. the chemical compound and the oxidation state of the metal, as well as the bioavailability of these metal species for organisms. In the environment biogeochemical transformations of metal species have to be taken into account. For example in aquatic systems the inorganic mercury species Hg2+ can be transformed by microorganisms into highly toxic methylmercury (MeHg) that represents the most environmental concern regarding this element [2]. Another example are acid mine drainage waters which are acidic effluents from abandoned mines which can contain very high amounts of arsenic. Biogeochemical processes involving microorganisms oxidize arsenite (AsO33−) to arsenate (AsO43−) together with the oxidation of iron (Fe2+ to Fe3+) resulting in As-Fe coprecipitation and thus the formation of the As(V)–Fe(III) hydroxysulfate sediments which reduce drastically the bioavailability of As [3].
Beside other toxic effects, metals can for example interfere with intracellular detoxification mechanisms of organic pollutants and thus amplify the toxicity of these compounds. Glutathione transferases (GSTs) play a key role in the detoxification of organic xenobiotics as well as endobiotic metabolites. When metals enter an organism, protective mechanism against oxidative stress and other detrimental effects involve also the increase of GST activity (for example in plants see [4]). However, there is increasing evidence that metals at toxic concentrations affect GSTs either by direct inhibition of enzyme activity or indirectly by decreasing the concentration of the GST substrate reduced glutathione (GSH, Fig. 1). The latter is involved in the cellular defense against metals by high chemical affinity to bind to soft metal ions, like Hg2+ and Cd2+ and/or metal-induced oxidative stress by changing the GSH/GSSG equilibrium [5,6]. As consequence, metal-induced inhibition of GSTs interferes with intracellular detoxification of organic xenobiotics or endobiotic metabolites which may lead to unpredictable toxicological consequences for organisms. This fact is of particular importance as under ecological conditions organic contaminants are often found together with metal contaminants [7,8].
Our review gives a brief overview on the role of GST in organisms and discusses recent data for both in vivo and in vitro inhibitory effects on animal and plant GSTs by toxic metals.
Section snippets
Characteristics of glutathione transferase and its role in biological systems
The glutathione transferase (formerly reported as glutathione S-transferases, EC 2.5.1.18) supergene family is composed of several isoenzymes which are involved in phase II detoxification of electrophilic xenobiotics and endogenous compounds in procaryotes [9,10] and eucaryotes including non-mammalian vertebrates [11], mammals and humans [12,13] and plants [[14], [15], [16]]. GSTs catalyze the conjugation of organic compounds to the nucleophilic sulfur of the major intracellular thiol compound,
Inhibition of GST by toxic metals in man, animals and plants
A principal function of the GST enzymes is the detoxification of xenobiotic substances by catalysing their conjugation with glutathione. This GST activity can be interfered by metals which may lead to detrimental toxic effects for the organism (Fig. 1). Data on in vivo and in vitro inhibitory effects of metal on GSTs are summarized in Table 1. In most of the studies the influence of toxic metals or surplus essential biometals to total GST activity was determined by measuring the absorbance
Conclusions
Metals represent a major ecological concern because they can accumulate in organisms in the food web and finally, they can be a threat to human health. Impact of metals to aquatic and terrestrial ecosystems at sub-lethal contaminant concentrations can cause biological responses of the glutathione antioxidative network including glutathione transferases in organisms living in polluted habitats. On cellular level, metals are able to inhibit different intracellular processes such as enzyme
Declaration of Competing Interest
The authors declare no conflict of interests.
Acknowledgements
This work was supported by the bilateral (German-French) DAAD - Campus France program PROCOPE funded by the German ‘Bundesministerium für Bildung und Forschung (BMBF)’, the French ‘Ministère des Affaires étrangères et du développement International (MAEDI)’ and ‘Ministère de l’Education nationale, de l’Enseignement supérieur et de la Recherche (MENESR)’.
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