Possible role of Ca2+ in heavy metal cytotoxicity.
1. Organic xenobiotic metabolism often results in oxidative stress, involving GSH depletion, alteration of thiol/disulphide balance and peroxidation of membrane lipids. These events can lead to the disruption of Ca2+ homeostasis, through impairment of the Ca2+ translocases present in cellular membranes. Inhibition of the activity of Ca,Mg-ATPases due to oxidation of their SH groups would lead to uncontrolled rises in cytosolic Ca2+ levels resulting in loss of cell viability. 2. These observations seem to be of interest when interpreting the biochemical mechanisms of heavy metal cytotoxicity. Since these cations (such as Hg2+, Cu2+, Cd2+ and Zn2+) have an extremely high affinity for SH groups, they may affect the function of SH containing proteins, such as the Ca,Mg-ATPases, as in the case of oxidative stress. 3. Results are reported indicating that Hg2+ may stimulate Ca2+ influx through voltage-dependent channels in different experimental systems. Moreover, evidence is presented that heavy metals can inhibit Ca,Mg-ATPase activity and affect mitochondrial functions in the cells of different organisms. 4. The possibility that heavy metal cytotoxicity is mediated through disruption of Ca2+ homeostasis is discussed.
Viarengo
A
A
Istituto di Fisiologia Generale, Università di Genova, Italy.
Nicotera
P
P
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008670:Metals / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects
D008670:Metals; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium