Inhibitory effect of metals on animal and plant glutathione transferases

Abstract

Glutathione transferases (GSTs) represent a widespread enzyme superfamily in eukaryotes and prokaryotes catalyzing different reactions with endogenous and xenobiotic substrates such as organic pollutants. The latter are often found together with metal contamination in the environment. Besides performing of essential functions, GSTs protect cells by conjugation of glutathione with various reactive electrophiles. The interference of toxic metals with this functionality of GSTs may have unpredictable toxicological consequences for the organisms. In this review results from the recent literature are summarized and discussed describing the ability of metals to inhibit intracellular detoxification processes in animals and plants.

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.