Metallothionein protection of cadmium toxicity.
The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases biliary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cd-induced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases are devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MT-transgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity.
Klaassen
Curtis D
CD
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA. cklaasse@kumc.edu
Liu
Jie
J
Diwan
Bhalchandra A
BA
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced / Q000378:metabolism; D011485:Protein Binding
D004785:Environmental Pollutants; D002104:Cadmium; D008668:Metallothionein