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Induction of Metallothionein in HeLa Cells by Dexamethasone and Zinc

1981; Wiley; Volume: 113; Issue: 2 Linguagem: Inglês

10.1111/j.1432-1033.1981.tb05062.x

1432-1033

Michael Karin, Harvey R. Herschman,

Aluminum toxicity and tolerance in plants and animals

Metallothioneins are induced by both Zn 2+ and dexamethasone in HeLa cells grown in serum‐free medium. Dexamethasone is able to induce metallothionein synthesis in HeLa cells in virtually zincfree medium ([Zn 2+ ] = 0.1 μM). The presence of dexamethasone does not shift the dose/response curve for metallothionein induction by Zn 2+ , further indicating that the two inducers work through independent mechanisms. Dexamethasone stimulates Zn 2+ uptake 1.7‐fold over 24 h. However, there is no increase in Zn 2+ uptake during the first 4 h. In contrast, metallothionein synthesis in response to either Zn 2+ or dexamethasone is clearly observable within 4 h of exposure to either inducer. The increased intracellular 65 Zn 2+ content observed at 24 h is completely accounted for by the increased level of metal bound to metallothionein. In a continuous labeling experiment the rate of synthesis of metallothionein reached a steady state after about 4 h, in response to either inducer. The lag period was identical for both dexamethasone and Zn 2+ , with similarly shaped induction curves. Induction by dexamethasone, but not by Zn 2+ , was inhibited by progesterone. Zn 2+ and dexamethasone appear to induce metallothionein synthesis in HeLa cells by mechanisms independent of one another.