Cadmium accumulation in neuronal cells leads to essential metals imbalance and zinc transporters dysregulation

The heavy metal cadmium (Cd), a natural element of the Earth's crust released into the environment through both natural processes and anthropogenic activities, is ranked 7th on the ATSDR Substance Priority List of hazardous substances. Its low excretion rate from human body and its long biological half-life (10-30 years) lead to Cd heavy accumulation in organisms. Although Cd carcinogenicity is well recognized, the neurotoxicity and damage to the nervous system still require further investigation. The interference with essential element homeostasis, referred as dyshomeostasis, is one of Cd neurotoxic mechanisms and its interference on specific ions balance could play a key role in the process of neurodegenerative diseases. In this study Cd possible impact on the balance of essential elements was evaluated in human neural SH-SY5Y cells, by exposing the target cells to low Cd concentrations (0.1-5 mu M) for 24 h, 48 h and 6 days. Cd accumulates inside the cells in a time and dose dependent manner with dysregulation of both zinc and iron homeostasis and induction of heme oxygenase 1 expression. Moreover, zinc transporters ZnT1 and ZnT2 are upregulated, while the iron transporter DMT1 is downregulated. In conclusion our data show that even low, sublethal cadmium concentrations are effective in inducing dyshomeostasis of essential metals involved in important neuronal functions.