Multiple roles of cadmium in cell death and survival

Cadmium is a toxic metal with no known biological function. It is increasingly important as an environmental hazard to both humans and wildlife, and it exemplifies the double edged nature of many toxic substances. Thus, on the one hand cadmium can act as a mitogen, stimulate cell proliferation, inhibit apoptosis, inhibit DNA repair, and promote cancer in a number of tissues. On the other hand, it causes tissue damage, notably in the kidney, by inducing cell death. At low and moderate concentrations in cell culture systems (e.g., 0.1–10 μM) cadmium primarily causes apoptosis, and at higher concentrations (>50 μM) necrosis becomes evident. This generalization appears to hold in vivo. There is also evidence of cadmium-induced autophagy, although whether this is a direct cause of cell death remains uncertain. After discussing these generalities, this review considers the details of apoptotic death, and its inhibition, in renal mesangial cells. We also present evidence for the effect of environmental exposure to cadmium in affecting renal function, and in particular review the evidence for the role of the mesangial cell in cadmium nephrotoxicity.