Metallothioneins and diseases with special reference to cadmium poisoning

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