PMC:1253828 / 35980-37758 JSONTXT

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Furthermore, metallothioneins provide protection against oxidative stress (1,17). In addition to metallothioneins, glutathione was postulated as a first line of defense against cadmium toxicity (77). Glutathione efficiently complexes cadmium (78) and scavenges free radicals and other reactive oxygen species directly, and indirectly via enzymatic reactions (45). In such reactions, glutathione is oxidized and has to be regenerated by glutathione reductase. Also, glutathione-S-transferases mediate the conjugation of various electrophiles to glutathione. The observed cadmium-induced upregulation of Gclc, Gsr and Gstm4 supports the importance of glutathione in the cellular cadmium response. The enhanced sensitivity to cadmium toxicity that we found for mouse embryonic fibroblasts upon a combination of Mtf1 deletion and depletion of glutathione further corroborates the importance of MTF-1 and its target genes as well as reduced glutathione for an efficient anti-cadmium 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