Hepatocellular copper toxicity and its attenuation by zinc

M. L. Schilsky, R. R. Blank, M. J. Czaja, Mark A Zern, I. H. Scheinberg, R. J. Stockert, I. Sternlieb

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Abstract

We studied the mechanisms by which excess copper exerts, and zinc mitigates, toxic effects on HepG2 cells. Survival and cell growth were reduced in media containing >500 μM copper chloride for 48 h; LD50 was 750 μM. At 1,000 μM copper for 1 h, there was a general reduction of protein synthesis, and no recognizable changes in cellular ultrastructure. Incubation of cells with 200 μM zinc acetate before exposure to copper, raised the LD50 for confluent cells to 1,250 μM copper chloride, improved protein synthesis, and increased synthesis of a 10-kD protein, apparently metallothionein. The mitigation, by zinc, of copper's toxicity may in part be mediated through induction of this protein in the hepatocyte.

Original languageEnglish (US)
Pages (from-to)1562-1568
Number of pages7
JournalJournal of Clinical Investigation
Volume84
Issue number5
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Schilsky, M. L., Blank, R. R., Czaja, M. J., Zern, M. A., Scheinberg, I. H., Stockert, R. J., & Sternlieb, I. (1989). Hepatocellular copper toxicity and its attenuation by zinc. Journal of Clinical Investigation, 84(5), 1562-1568.