Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

Figure 1

Proposed mechanism for the prooxidative action of Hg(II). Mercury ion (Hg²⁺) is shown to bind to the dissociated form of the selenol (-Se⁻) moiety of the catalytic selenocysteine residue of glutathione peroxidase and thioredoxin reductase thereby inactivating the enzymes; the result is an enhanced level of reactive oxygen species because of their lower inactivation. The catalytic cycles of the two antioxidant enzymes are also shown: glutathione peroxidase converts H₂O₂ in 2 H₂O molecules at expense of 2 reduced glutathione molecules (GSH), which are oxidized to GSSG; thioredoxin reductase reduces oxidized thioredoxin (Txr) at the expense of NADPH thereby enabling reduced Txr to preserve the redox state of protein cysteines (P) from the H₂O₂-mediated oxidation. Mitochondria is illustrated as a major intracellular producer of ROS generated from electron leaks from the respiratory chain (RC) to O₂ to form the superoxide anion (O₂^•−). This is further converted in H₂O₂ by the mitochondrial isoform of the superoxide dismutase (SOD₂).