Stress proteins metallothionein

Metallothionein content MT Stress protein Cd, Cu, Zn, Hg, oxidative stress Liver tissue 6-15... 

The response of cells to stress (including reactive oxygen species and reactive metabolites) includes the upregulation of synthesis of stress proteins metallothioneins hsplOO, hsp 90, hsp70, hsp60, and hsp27. 

The stress-related proteins discussed above are induced by a variety of stressors. However, other groups of proteins are induced by specific materials. Metallothioneins are proteins that are crucial in reducing the effects of many heavy metals. Originally evolved as important players in metal regulation, these proteins sequester heavy metals and thereby reduce their toxic effects. Metallothioneins are induced and like many proteins can be identified using current immunological techniques. 

Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219 1-14 Hamer DH (1986) Metallothionein. Annu Rev Biochem 55 913-951 Hamet P (1992) Abnormal hsp70 gene expression its potential key role in metabolic defects in hypertension. Clin Exp Pharmacol Physiol [Suppl] 20 53-59 Hansen DK, Anson JF, Hinson WG, Pipkin JL Jr (1988) Phenytoin-induced stress protein synthesis in mouse embryonic tissue. Proc Soc Exp Biol Med 189 136-140... 

Besides the intoxication by heavy metal, the stress caused by free radicals represents next threat for organism. The role of MT in this field was therefore investigated too [162]. Damage of complexes of plant thiols (metallothionein-like proteins) and Zn and Cd ions by reductive radical stress was investigated by Raman spectroscopy [7, 162]. Cysteine moieties have been shown to be among the most sensitive toward radical attack. The authors concluded that MT residues are more sensitive to the reductive radical attack when the protein... 

Elevated metallothionein levels are not necessarily indicative of heavy-metal insult. Starcher et al. (1980) show that liver metallothionein levels in mice are elevated following acute stress or starvation, and that this effect is blocked by actinomycin D, a protein synthesis inhibitor. It is further emphasized that not all zinc-binding proteins are metallothioneins (Webb etal. 1985 ... 

These proteins are important for binding potentially toxic metals such as cadmium, mercury, and lead, which all bind to sulfydryl groups. Consequently, the binding and removal of these metals are protective functions. Metallothioneins are markedly induced by cadmium exposure and the small protein, rich in SH groups, can then sequester the metal. They also may have a protective role in oxidative stress and protect redox-sensitive processes. The protein also has a role in cadmium nephrotoxicity (see chap. 7). 

The metabolism of zinc is influenced by hormones, stress situations, lipopolysaccharides, toxins, oxygen radicals, lipid peroxidations, etc. This may lead to fluctuations in the zinc concentration, mainly due to the induction of metallothioneine (MT), which is a transport and intracellular depot protein. One third of this protein consists of cysteine, which binds zinc, copper, cadmium, cobalt and mercury. This protects the body from toxic heavy metal... 

Nutritional status Many antioxidants are present in the diet (e.g., vitamin E, vitamin C, peptides for the synthesis of glutathione, trace metals, and minerals like zinc). However, poor nutrition or malabsorption leads to deficiency of these key vitamins and antioxidants. This may impair the antioxidative defense capacity, leading to drug-induced oxidative stress and lower threshold for DILL In a preclinical study, a mere 1.6- and 2.1-fold increase in liver zinc content was associated with an increase in liver metallothionein between 50- and 200-fold.38 Metallothionein is a key antioxidant protein in vivo capable of scavenging most common kinds of oxidative species.39 It is therefore conceivable that a lack of sufficient dietary available zinc could compromise a patient s hepatic metallothionein levels and his or her antioxidant reserve capabilities in liver. 

---