Divalent metal transporter 1 in lead and cadmium transport

Abstract

The effect of exposure to cadmium (Cd) and lead (Pb) on human health has been recognized for many years and recent information suggests that minimal exposure levels are themselves too high. Common scenarios for Pb exposure include occupational, residential, and/or behavioral (hand-to-mouth activity) settings. The main source of Cd exposure for nonsmokers is dietary, through plants or animals that accumulate the metal. Specific cellular importers for Pb and Cd are unlikely as these metals are nonessential and toxic. Accordingly, in the intestine, the operational mechanism is assumed to be inadvertent uptake through pathways intended for essential nutrients such as iron. Results from experimental and epidemiological studies indicated that diets low in iron (Fe) result in increased absorption of Pb and Cd, suggesting common molecular mechanisms of Cd and Pb transport. Indeed, recent mechanistic studies found that the intestinal transporter for nonheme iron, divalent metal transporter 1 (DMT1), mediates the transport of Pb and Cd. DMT1 is regulated, in part, by dietary iron, and chemical species of Cd and Pb that are transported by DMT1 would be made available through digestion and are also found in plasma. Accordingly, the involvement of DMT1 in metal uptake offers a mechanistic explanation for why an iron-deficient diet is a risk factor for Pb and Cd poisoning. It also suggests that diets rich in iron-containing food could be protective against heavy metal poisoning.