Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection.

Abstract

Hypozincemia was induced in rats by Salmonella typhimurium and live vaccine strain Francisella tularensis (LVS) infections. Hepatic synthesis of zinc-binding proteins (ZBP) was studied in order to elucidate the mechanisms involved in the redistribution of zinc from plasma to liver occurring during infectious illness. ZBP, labeled in vivo with 65Zn, were isolated and identified as metallothioneins based, in part, on their heat stability, dimorphism, and amino acid composition. Cysteine was the major amino acid found in both forms of metallothionein and constituted 28-31% of total residues. The apparent half-life of these proteins as measured by disappearance of 65Zn was determined to be 19 h in a relatively mild infection (LVS) and 38 h in a more severe S. typhimurium infection. Results provide evidence that metallothioneins not only have the previously postulated regulatory role in normal zinc homeostasis but are intimately involved in the zinc redistribution occurring during the acute stage of infectious illness.

Ligand substitution reactions of metallothioneins with EDTA and apo-carbonic anhydrase.

“…The study of metallothionein function has been stimulated recently by the demonstration that Zn-thionein is a normal constituent of cells under various physiological conditions including cancer (3)(4)(5)(6)(7)(8). The question of its role in metabolism arises.…”

“…Chemical studies of metallothionein reactions have not progressed far beyond the first report after its identification in cells (2). Hence, although metallothionein binds cadmium after exposure of the host to this toxic metal and recently has been shown to bind zinc and copper under various physiological conditions, no bioinorganic studies have provided a foundation for reasonable hypotheses as to the meaning of these results (3)(4)(5)(6)(7)(8). Such studies are difficult because there are seven sites that may be occupied by a combination of Zn and Cd ions.…”

Dietary Zinc Supplementation Ameliorates LPS-Induced Teratogenicity in Mice

“…Previous studies employing various teratogens(including urethane, ␣-hederin, 6-mercaptopurine, TNF-␣, and valproic acid) suggested that MT and its associated changes in maternal-fetal Zn distribution were the key mediators of teratogenicity (19 -24). We and others have shown that alcohol (25) and LPS (26,27) are all potent inducers of MT in the liver resulting in sequestration of plasma Zn in the liver, with a consequent decrease in plasma Zn concentration.…”

Metallothionein-Null Mice Are Sensitive to Endotoxine/D-Galactosamine-Induced Hepatotoxicity.

“…8,9) Metallothionein (MT), which is a low-molecular weight, cysteinerich, metal-binding protein, is known to be induced during the acute-phase response. 10) MT induction during the acute-phase response is also mediated by IL-6. 11) However, the specific function of MT during the acute-phase response remains to be elucidated.…”