Endotoxin-Induced Changes in Copper and Zinc Metabolism in the Syrian Hamster

Abstract

The temporal response of zinc and copper metabolism to endotoxin administration was examined in Syrian hamsters over a 144-hour period. Serum copper was significantly elevated at 12, 24 and 72 hours after endotoxin, whereas serum zinc was reduced 4-48 hours after treatment. A brief elevation (8 hours) in liver copper concentration and a sustained (72 hours) increase in liver zinc concentration were also observed. The amount of zinc associated with liver metallothionein (MT) progressively increased with time, to a plateau by 24 hours and persisted at the elevated level until 72 hours after endotoxin treatment. In vitro translation of poly (A)+ RNA from liver polyribosomes showed that following endotoxin treatment MTmRNA activity was maximally elevated 6 hours after endotoxin administration and remained elevated 24 and 48 hours thereafter. Slab gel electrophoresis of serum proteins indicated changes in a stainable protein comigrating with purified ceruloplasmin after endotoxin administration. Pooled gingival tissue from endotoxin-treated hamsters demonstrated a consistently elevated copper content 12-144 hours after treatment. Endotoxin isolated from Bacteroides melaninogenicus was more effective in elevating gingival and serum copper and gingival zinc than Escherichia coli endotoxin. It was concluded that endotoxin administration elicits responses that result in enhanced metaollthionein mRNA activity. In addition, Cu and Zn concentrations in serum, liver and gingival tissue are influenced by different endotoxins to different degrees.

Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

“…This effect of endotoxin may be species-or age-specific. For example, endotoxin administration to Syrian hamsters increased serum Cu concentration but did not decrease Cu concentrations in liver (6). The effects of LPS on the concentrations of Zn and Cu in liver cytosol and the binding of these metals to MT should be examined in context of the changes in Zn and Cu distribution and binding that occur in liver in early postnatal life.…”

“…In rats and Syrian hamsters, endotoxin treatment increases Zn and decreases Cu concentrations in liver and decreases Zn and increases Cu concentrations in plasma (6,7). At the cellular level, endotoxin treatment increases the amount of Zn bound to MT, a cytosolic transition metal-binding protein, in the liver (8) and in cultured hepatocytes (9) and increases the urinary excretion of MT (10).…”

“…Because endotoxin increases MT gene transcription (6,7) and because this protein sequesters both Zn and Cu intracellularly (13), the possibility that changes in the Zn and Cu distribution among tissues and their binding to MT were associated with endotoxin exposure was investigated. Thymic growth in endotoxin-treated neonatal mice was examined, because decreased Zn and Cu bioavailability either in utero or in early postnatal life can affect thymic growth and development and diminish immunoresponsiveness (1 4-18).…”

Metallothionein — Aspects related to copper and zinc metabolism

“…A plethora of studies has shown metallothionein-bound zinc and copper is responsive to dietary supplies of these nutrients (Richards and Cousins, 1976;Bremner and Davies, 1976;McCormick et aI., 1981;Whanger and Ridlington, 1982). Increased binding of zinc to metallothionein is brought about by food restriction (Bremner and Davies, 1975;Richards and Cousins, 1976), environmental stresses (Oh et al, 1978), infectious agents (Soboscinski et al, 1978), liver regeneration (Ohtake et al, 1978) and endotoxin administration (Etzel et al, 1982). Metallothionein messenger RNA is increased following treatment with zinc (Shapiro et al, 1978;Durnam and Palmiter, 1981 ;McCormick et aI., 1981;Menard et al, 1981;Swerdel and Cousins, 1982), copper (Mercer et al, 1981;Durham and Palmiter, 1981) and cadmium (Anderson and Weser, 1978;Ohi et al, 1981), endotoxin (Etzel et al, 1982), glucocorticoids (Etzel et al, 1979;Hager and Palmiter, 1981) as well as during fetal development (Ouellette, 1982).…”

Driving Along the Zinc Road

“…The arrival of Mark Failla, my first postdoctoral associate, allowed us to study the hormonal regulation of zinc and cadmium metabolism under in vitro conditions (13). Charlie McCormick and Ken Etzel joined as postdoctoral associates and worked on induction of MTmRNA as modulated by the dietary zinc level (27) and endotoxin/hormonal control of zinc metabolism (12), respectively.…”