Selective enhancement of metallothionein mRNA expression by copper in primary cultured liver parenchymal cells of LEC rats.

Abstract

Mechanisms for the abnormal copper (Cu) accumulation in the liver of LEC rats were examined using primary cultured liver parenchymal cells prepared from mutant LEC rats and those from control LEA rats (original strain). The Cu and metallothionein (MT) mRNA levels in the liver of LEC rats were caused to decrease to the same levels as those of LEA rats by removing Cu in vivo selectively with tetrathiomolybdate. Cu was taken up by LEC rat cells to the same extent as LEA rat cells by exposure to low medium Cu and to a higher extent by exposure to high medium Cu, while the MT mRNA level in LEC rat cells increased dose-dependently at a much higher rate than that in LEA rats. MT mRNA levels in both cells were comparable by exposure to cadmium, zinc and dexamethasone. The results indicate that expression of MT mRNA is selectively enhanced by Cu in LEC cells despite the fact that uptake of Cu is comparable with normal cells.