Metallothioneins and diseases with special reference to cadmium poisoning

Metallothionein (MT) a low molecular weight metal binding protein, is involved in several human diseases. Brain tissue from Alzheimer's patients contains lower concentrations of Growth Inhibitory Factor or MT-3. Induction of MT by bismuth increases resistance to renal toxicity of cis-platinum and may be advantageous in cancer therapy. Cadmium exposure induces MT-synthesis in liver, binding Cd and protecting against acute toxicity. Cd-MT is released from liver into plasma, filtered in renal glomerulus and absorbed in tubules. Lysosomal breakdown of MT releases toxic Cd. This mechanism explains renal tubular damage after long-term exposure to Cd. Impaired tubular regulation of calcium and vitamin D metabolism contributes to the development of the adverse effects on the skeleton. Quantitative, specific polymerase chain reaction (PCR) studies showed increased expression of mRNA of MT in testicles after Cd exposure, supporting the notion that MT increases cellular resistance to metals and protects from Cd toxicity. This idea was advanced by one of the present authors thirty years ago.