Constitutive expression of metallothionein-III (MT-III), but not MT-I, inhibits growth when cells become zinc deficient

Toxicol Appl Pharmacol. 1995 Nov;135(1):139-46. doi: 10.1006/taap.1995.1216.


BHK cells were stably transformed with plasmid constructs that allowed constitutive expression of either mouse metallothionein-I (MT-I) or MT-III to determine whether these isoforms have different physiological properties. Cells expressing equivalent amounts of MT-I or MT-III could grow in 60-fold more cadmium than nontransfected cells and they were 2- to 3-fold more resistant to zinc, copper, and cobalt. The results suggest that the two MT isoforms detoxify these metals similarly. MT-III reduced the amount of zinc available to activate a zinc-sensitive reporter gene; MT-I actually increased the expression of the reporter gene at low concentrations of zinc. Cells expressing MT-I or MT-III also responded differently to zinc deficiency. When cells expressing MT-I were deprived of zinc, the amount of MT-I protein declined to undetectable levels, even though MT-I mRNA was still abundant, and cell proliferation was unaffected. In contrast, when cells expressing the MT-III gene were deprived of zinc, cell proliferation was arrested and MT-III protein persisted. These results suggest that MT-I does not compete with essential zinc-requiring proteins and is degraded, whereas MT-III competes for zinc and exacerbates zinc deficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division / drug effects
  • Cell Line
  • Cricetinae
  • Drug Resistance / genetics
  • Growth Inhibitors / genetics
  • Growth Inhibitors / metabolism*
  • Growth Inhibitors / toxicity
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Metallothionein / toxicity
  • Metallothionein 3
  • Metals / toxicity
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / toxicity
  • Zinc / deficiency*
  • Zinc / toxicity


  • Growth Inhibitors
  • Metallothionein 3
  • Metals
  • Nerve Tissue Proteins
  • Metallothionein
  • Zinc