Jc. Philcox et al., ENDOTOXIN-INDUCED INFLAMMATION DOES NOT CAUSE HEPATIC ZINC ACCUMULATION IN MICE LACKING METALLOTHIONEIN GENE-EXPRESSION, Biochemical journal, 308, 1995, pp. 543-546
The action of endotoxin lipopolysaccharide (LPS) on hepatic Zn uptake
was examined in mice lacking expression of metallothionein (MT)-I and
MT-II genes. Hepatic Zn concentrations, which in normal control mice i
ncreased by a mean 29 % (MT elevated 20-fold) 16 h post-LPS exposure,
did not increase in MT-null mice. Plasma Zn fell by 68 % in controls a
nd 32 % in MT-null mice. The time course of LPS action in normal mice
was characterized by a rapid reduction (- 74 % at 4 h, - 81 % at 8 h)
and partial recovery (- 39 % at 24 h) in plasma Zn, with a progressive
increase over 24 h in hepatic concentrations of MT (by 36-fold) and Z
n (by 40 %). In contrast, the MT-null mice had a linear decrease in pl
asma Zn (-15 % at 8 h, -41 % at 24 h) and early loss of Zn from the li
ver. The Zn changes seen in MT-null mice were largely attributable to
LPS-associated anorexia. Food deprivation (20 h) alone caused respecti
ve 14 % and 30 % decreases in hepatic and plasma Zn concentrations and
a 27 % reduction in total liver Zn reserves, whereas fasted normal mi
ce conserved Zn with a 4-fold increase in hepatic MT. This study confi
rms that MT synthesis is essential for endotoxin-induced liver Zn accu
mulation.