Metallothionein mRNA induction in HeLa cells in response to zinc or dexamethasone is a primary induction response

Abstract

Metallothioneins (MTs) are low molecular weight, heavy metal binding proteins unique in their high cysteine content and high affinity for Zn2+, Cd2+, Hg2+, Ag2+ and Cu2+ (refs 1--3). The synthesis of MTs is induced by zinc or cadmium in the liver and kidney and in cultured cells. More recently MT induction by the steroid hormone dexamethasone (Dex) has been demonstrated in HeLa cells and adrenalectomized rats. Because glucocorticoid hormones lead to an intracellular accumulation of zinc, the question arises of whether the induction of MT gene expression by steroids is a 'primary induction response' (ref. 18), or due to elevated intracellular Zn2+. The glucocorticoid-induced transport of Zn2+ is dependent on concurrent protein synthesis. We now show that, in contrast to glucocorticoid-stimulated Zn2+ transport, the Zn2+ and Dex induction of translatable MT-mRNA is independent of concomitant protein synthesis but not RNA synthesis; that is, MT induction by either agent is a primary induction response.

Activation of gene expression by metal-responsive signal transduction pathways.

“…Exposure to metals, organic chemicals, physical stress, intracellular damage, and physiologic agents causes an increase the steady-state level of MT mRNA (5,(37)(38)(39)(40). In addition, several of these nonmetal stressors activate MT transcription via MREs (10,22,41,42).…”

Dexamethasone regulation of the expression of cytokine mRNAs induced by interleukin‐1 in the astrocytoma cell line U373MG

“…It has been shown that mRNA induction by dexamethasone does not require de novo protein synthesis [36]. However it is not clear whether dexamethasone inhibition of mRNA induction requires de novo protein synthesis or not.…”

Control of gene expression by glucocorticoid hormones

“…Reference Diesterhaft et al (1980), Olson et al (1980) Danesch et al (1983) Sarkar & Griffith (1976) McGinnis & de Vellis (1978) Chen & Feigelson (1979) Karin et al (1980), Mayo & Palmiter (1981) Mierendorf & Mueller (1982)…”