Evolution of metallotionein isoforms complexes in hepatic cells of Mus musculus along cadmium exposure

Abstract

Characterization of Cd-binding proteins has great analytical interest due to the high toxicity of Cd to living organisms. Metallothioneins (MTs), as Cd(II)-binding proteins are of increasing interest, since they form very stable Cd chelates and are involved in many detoxification processes. In this work, inductively coupled plasma octopole reaction cell mass spectrometry and nanospray ionization time-of-flight mass spectrometry were used in parallel and combined with two-dimensional chromatography: size exclusion followed by reversed-phase high performance liquid chromatography, to study metal complexes of MT isoforms produced in hepatic cytosols of Mus musculus during exposure experiments to Cd. Exposure experiments were carried out by subcutaneous injection of a growing dose of the toxic element ranging from 0.1 to 1.0 mg of Cd per kg of body weight per day during 10 days. A control group and three exposure groups at days 2, 6 and 10 of exposure were studied, and different cadmium, copper and zinc complexes with MTs isoforms were isolated and characterized from the two most exposed groups. The results allow gaining insight into the mechanisms involved in metal detoxification by MTs, showing the changes in the stoichiometry of metal complexes-MTs along cadmium exposure.

Cadmium Protection Strategies—A Hidden Trade-Off?

“…In terrestrial gastropods, the evolution of a MT isoform showing an extraordinary Cd 2+ -binding specificity was observed [ 89 ]. A recent study on mammalian MT1A revealed that the domain-specific order of the binding reaction and not the binding affinities account for the binding of zinc or Cd 2+ [ 90 ], whereas it had already been shown that MT1 is more significantly sequestering Cd 2+ than MT2 [ 91 ]. Several examples show that MT isoforms evolved to take over isoform-specific functions like Cd detoxification in mollusks [ 92 , 93 ], sea urchins [ 94 ], Drosophila [ 95 ], C. elegans [ 96 ], and Tetrahymena species [ 97 , 98 ].…”

Functional genomics and metabolomics reveal the toxicological effects of cadmium in Mus musculus mice

“…3.3 Transcriptional profile in mouse following cadmium exposure Both Cd and ROS influence signal transduction processes via the modulation of transcription factors which lead to the transcriptional activation of different genes (Habeebu et al, 2000;Jara-Biedma et al, 2013 in the same range, demonstrating that the studied genes have a stable expression in these samples. From these results, we assumed that the study would not be exposed to misinterpretation by using sample pools.…”

“…Compared to controls, the livers of Cd-exposed mice showed an impressive and time-dependent increase of Mt-1 mRNA molecules. We have previously reported that Cd exposure also induce MT expression at the protein level, by coupling HPLC with ICP-MS and ESI-MS which permitted us to identify Cd complexes with MT isoforms induced in Mus musculus (Jara-Biedma et al, 2013).…”

Cadmium toxicity in Mus musculus mice based on a metallomic study. Antagonistic interaction between Se and Cd in the bloodstream

“…In relation to this, the induction of Cd and Zn-metallothioneins in mice (Mus musculus) exposed to higher concentrations of Cd has been reported, 33 and these experimental data confirm the antagonistic interactions among Cd, Zn, Cu, as well as the differential rate of excretion of these elements from kidney/liver under increasing exposure. 34 It is well known that Cd exposure causes change in the distribution of endogenous Zn and Cu in tissues and biological fluids, since both metals play a protective role against Cd toxicity, due to their contribution in MTs induction (Fig.…”