Heavy Metal Cytotoxicity in Marine Organisms: Effects on Ca²⁺ Homeostasis and Possible Alteration of Signal Transduction Pathways

Summary

The data reported show that heavy metals, such as Hg²⁺, Cu²⁺, Cd²⁺, and Zn²⁺, are able to affect the mechanisms of Ca²⁺ homeostasis. It has been demonstrated that heavy metals, probably interacting with the sulphydrylic groups of the membrane proteins involved in the structure of the Ca²⁺ channels, can enhance the flux of Ca cations through the plasma membrane, the membrane of calciosomes, and mitochondria.

Moreover, the high affinity of heavy metals for SH residues could explain the high sensitivity of Ca²⁺ ATPases to these metals. In fact, Ca²⁺ translocases contain SH groups critical for the enzyme activity.

In the case of Cu²⁺ this cation, probably through the production of oxygen radicals, stimulates the process of lipid peroxidation of cell membranes, possibly contributing to the alteration of structural and enzymatic proteins involved in Ca²⁺ homeostasis through the oxidation of the sulphydrylic residues. In addition, heavy metals are also able to inhibit the Na⁺ /K⁺ ATPase, a well-known SH-containing enzyme present in the plasma membrane. This is of particular interest considering that Na⁺ /K⁺ translocase regulates a Na⁺/Ca²⁺ exchanger, whose function in Ca²⁺ homeostasis has been demonstrated in the plasma membrane of many different cells.

The role of GSH and metallothioneins as important components of the cell mechanisms to reduce the cytotoxic effects of heavy metals has here also been described.

Data are also presented concerning the effects of heavy metals on the mechanism of signal transduction. It seems possible that the cations affecting Ca²⁺ homeostasis could render the cell no more sensitive to Ca-mediated hormones and external stimuli. In addition, heavy metals could exert a direct effect on different aspects of signal transduction pathways.