Metallothionein protection of cadmium toxicity

Abstract

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 billiary 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 Cdinduced 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 were 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 MTtransgenic 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.

MRP proteins as potential mediators of heavy metal resistance in zebrafish cells

“…In addition, chemical state of metals and the availability of substrates may restrict the efficiency of MRP transporters. It is known that cellular metals can bind to metallothionein (MT) to reduce the acute toxicity; while, heavy metals bound to MT leads to their accumulation in tissues and the long biological half-life in the body (Klaassen et al, 2009). Therefore, the overall outcome of heavy metal detoxification in organisms or cells is determined by the cooperation and balance among intracellular factors.…”

Microarray analysis of metallothioneins in human diseases—A review

“…At the protein level, MT has been examined as a marker of cancer [29] and also of metals' and toxic compounds' intoxication [30,31]. For these purposes, numerous analytical and biochemical methods are used [32,33], whereas the electrochemical ones seem to be the most sensitive [33][34][35].…”

Alteration in the activity of oxidative enzymes in the tissues of male wistar albino rats exposed to cadmium

“…It would not seem reasonable to exclude that this is connected with the induction of MT in the liver. Besides aiding the transport and distribution of Cd, MT also decreases its toxicity [1,[32][33][34]. Experimental evidence indicates that the liver is more efficient in the induction of MT than other organs [35].…”