BioMetals

, Volume 23, Issue 5, pp 877–896

Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals

Article

DOI: 10.1007/s10534-010-9336-y

Cite this article as:
Moulis, JM. Biometals (2010) 23: 877. doi:10.1007/s10534-010-9336-y

Abstract

The widespread occurrence of cadmium in the environment continues to pose a threat to human health despite attempts at limiting its technological uses. The biologically significant ionic form of cadmium, Cd2+, binds to many bio-molecules and these interactions underlie the toxicity mechanisms of cadmium. Some of the molecules specialized in the handling of alkaline earth (Mg2+, Ca2+) and transition metal ions (e.g. Zn2+, Cu2+/+, Fe3+/2+) should be particularly sensitive to the presence of Cd2+, because they enclose cationic sites to which the toxic metal can bind. The possible molecular targets of this kind for cadmium are considered herein. Whereas in vitro evidence for native cation replacement by Cd2+ in bio-molecules has been largely provided, the demonstration of such occurrences in vivo is scarce, with the notable exception of metallothionein. One reason might be that realistic low-level Cd2+ contaminations involve cellular concentrations far smaller than those of endogenous cations that usually saturate their binding sites. It is very likely that cadmium toxicity is most often mediated by biological systems amplifying the signals triggered by the presence of Cd2+. The interference of Cd2+ with redox sensitive systems acting at the transcriptional and post-transcriptional levels is instrumental in such processes. A better understanding of cadmium toxicity to tackle the environmental challenges lying ahead thus requires properly designed studies implementing biologically relevant cadmium concentrations on different cell types, improved knowledge of the homeostasis of essential metals, and use of these data in a theoretical framework integrating all cellular aspects of cadmium effects.

Keywords

Transition metals Iron Copper Manganese Reactive oxygen species Regulation Resistance mechanism 

Abbreviations

DMT1

Divalent metal-ion transporter 1 (SLC11A2)

FPN

Ferroportin (SLC40A1)

FT

Ferritin

Hepc

Hepcidin

IRP

Iron regulatory protein(s)

MAPK

Mitogen activated protein kinases

MT

Metallothionein(s)

MTF-1

Metal-response element-binding transcription factor

PKC

Protein kinase C

PPIX

Protoporphyrin IX

ROS

Reactive oxygen species

HO-1

Heme oxygenase 1

SOD

Superoxide dismutase

Tf

Transferrin

ZnT

Zinc transporter (SLC30)

ZIP

Zinc regulated and iron regulated metal transporter-like protein(s) (SLC39)

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  1. 1.Laboratoire de Chimie et Biologie des MétauxCEA-Grenoble, DSV, IRTSVGrenoble Cedex 9France
  2. 2.CNRS UMR5249GrenobleFrance
  3. 3.Université Joseph FourierGrenobleFrance