Showing papers by "Michael Karin published in 1981"

Induction of Metallothionein mRNA in HeLa Cells by Dexamethasone and by Heavy Metals

Abstract: Synthesis of metallothionein, a cysteine-rich heavy metal binding protein, is induced in cultured HeLa cells both by the heavy metals Cd2+, Zn2+ and Cu2+, and by the glucocorticoid hormone dexamethasone. The accumulation of [35S]cysteine-labeled metallothionein and the amount of translatable metallothionein mRNA show identical concentration dependences, in response to dexamethasone treatment and in response to zinc exposure. Induction of translatable metallothionein mRNA is rapid in response to both the metal and glucocorticoid inducers. Increased synthesis and accumulation of metallothionein in response to either metal or glucocorticoid exposure is regulated by the level of translatable metallothionein mRNA in HeLa cells.

Regulation of metallothionein synthesis in HeLa cells by heavy metals and glucocorticoids

Abstract: Metallothioneins (MTs) are low molecular weight, cysteine-rich proteins that bind heavy metals. MT induction occurs in liver in response to either heavy metal (Zn/sup + +/ or Cd/sup + +/) administration or stress. The synthesis of MT can also be induced by either heavy metals or glucocorticoid hormones in HeLa cells cultured in serum-free medium. Induction of MT by zinc is subject to desensitization. In contrast, dexamethasone (dex) induction results in a continued elevation in the rate of MT synthesis. The stability of MT is dependent on the availability of metal; consequently, MT induced by dex is degraded much more rapidly (half-life of 11 to 12 hours) than MT induced by elevated zinc levels (half-life of 36 to 38 hours). Removal of either inducer results in biphasic degradation curves, as apothionein and zinc come into balance. In contrast, deinduction kinetics for MT synthesis following removal of the two inducers (zinc and dex) are the same, with a half-life of two and one-half hours. Inhibition of RNA synthesis blocks deinduction after removal of inducer. Induction of MT occurs in a wide variety of species, from blue-green algae to man. This system should provide an excellent model for the comparative biochemistry ofmore » regulation of gene expression.« less