Rat Metallothionein Multigene Family

Andersen, Robert D.; Taplitz, S J; Birren, Bruce W.; Bristol, Gregory; Herschman, Harvey R.

doi:10.1007/978-3-0348-6784-9_35

Cited by 11 publications

(7 citation statements)

References 17 publications

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“…The number of isoforms varies between species and tissues, but there are only two MT proteins preferentially expressed in rat liver, namely MT-1 and MT-2 [2]. It has been proposed that these proteins play a major role in the control of intracellular metal concentrations and detoxification [3,4,5], but there is increasing evidence that they possibly have antioxidant functions in the cell [6,7].…”

Section: Introductionmentioning

confidence: 98%

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Mh¹,

Tam

Beattie³

et al. 1996

Biochemical Journal

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The expression of metallothionein (MT)-1 and -2 mRNAs in rat liver following administration of Cd or Cu was investigated using specific oligonucleotides. The specificity was confirmed using a competitive prehybridization assay. Cd injection caused a biphasic induction of both isoform mRNAs, whereas Cu induced a sustained, monophasic response. Analysis of polyribosomal RNA showed that, after both Cd and Cu treatments, the recruitment of MT-1 mRNA into polyribosomes paralleled the increase in transcription, but the increase of polyribosomal MT-2 mRNA was less than that of total MT-2 mRNA. This indicates that not all the MT-2 mRNA induced was translated, suggesting that there is translational control of MT-2 mRNA expression, but not of MT-1 mRNA. This hypothesis was supported by the observation that, after Cu treatment, the induction of MT-1 protein was induced to the same extent as MT-1 mRNA, whereas the total MT protein (MT-1 + MT-2) was increased far less (7-fold) than MT-2 mRNA (30-fold).

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Section: Introductionmentioning

confidence: 98%

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Mh¹,

Tam

Beattie³

et al. 1996

Biochemical Journal

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“…One might expect normally cryptic transcription initiation sites to be recruited in these circumstances. We have identified a promotor-like sequence 450 bp 5' to the authentic initiation site of the MT-I gene (34). This region can initiate transcripts after transfection of a plasmid carrying the MT-I gene into 293 cells.…”

Section: Discussionmentioning

confidence: 99%

“…S1 Analysis: A BglII digest of a plasmid containing the rat MT-I gene (33) and hybridized to 20 ug of cytoplasmic RNA overnight at 420. The probe extends 127 bp 5' to the transcription start site, and terminates 65 bases 3' to this site (34). Hybridization, Si nuclease digestion (Pharmacia-P-L Biochemicals), and electrophoresis were carried out as described (35).…”

Section: Methodsmentioning

confidence: 99%

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Regulation of the rat metallothionein-I gene by sodium butyrate

Birren

Herschman

1986

Nucleic Acids Research

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Sodium butyrate selectively induces accumulation of metallothionein-I (MT-I) RNA in H4IIE rat hepatoma cells. The induction is rapid; significant elevation in cytoplasmic MT-I RNA can be observed within three hours after exposure to 5 mM butyrate. Maximal levels of MT-I RNA are obtained after eight hours. Butyrate stimulates MT RNA accumulation in the absence of de novo protein synthesis, indicating that MT induction by butyrate is not a distal step in a cascade of gene activation events. Butyrate blocks the induction of tyrosine amino transferase by dexamethasone. In contrast, butyrate and dexamethasone induced MT RNA elevations are additive. Butyrate induced MT-I RNA transcripts initiate at the correct start site. Measurements of the transcriptional activity of the MT-I gene indicate that butyrate stimulates MT-I transcription. The rapid, direct nature of the induction of MT-I by butyrate, combined with the extensive characterization of the metallothionein gene, provide an excellent system in which to study the effects of butyrate on a small, well-defined, responsive region of chromatin.

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“…The equality of amounts of RNA transferred to the membrane was determined by ultraviolet illumination (UV) following ethidium bromide staining. After prehybridization, filters were hybridized with MT-1 (Anderson et al, 1983), MT-2 (Anderson et al, 1987) or a-tubulin (Cleveland et al, 1980) cDNA probes overnight at 42°C. cDNA probes were labeled with Ic~-~'PI~CTP to a specific activity of 2-5 x 108cpm/yg of DNA, using a primer extension kit (Amersham).…”

Section: Methodsmentioning

confidence: 99%

Amplification of the metallothionein‐1 and metallothionein‐2 genes in copper‐resistant hepatoma cells

Czaja

Weiner

Freedman

1991

Journal Cellular Physiology

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The molecular basis for increased metallothionein concentrations in copper-resistant hepatoma cells was examined. The copper-resistant cell line HAC600, which is maintained in 600 microns copper, had increased steady-state mRNA levels for both the metallothionein-1 (MT-1) and the metallothionein-2 (MT-2) genes. Levels of mRNA were increased 11-fold for MT-1 and 15-fold for MT-2, with no significant change in alpha-tubulin mRNA content. HAC600NM cells, which are copper-resistant cells kept in a normal copper concentration for over 1 year, also had eight- and tenfold increases in MT-1 and MT-2 mRNA levels. Nuclear run-on assays showed that MT-1 and MT-2 gene transcription was increased nine- and eightfold in HAC600 cells and seven- and tenfold in HAC600NM cells, respectively. Southern blot analysis showed amplification of both metallothionein genes in HAC600 and HAC600NM cells. Thus the molecular basis of increased metallothionein in these hepatoma cells involved a stable gene amplification of both MT genes. The greater increase in metallothionein mRNA levels in HAC600 cells relative to the changes in transcription suggests that posttranscriptional mechanisms of gene regulation may also be acting in these cells.

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Rat Metallothionein Multigene Family

Cited by 11 publications

References 17 publications

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

Regulation of the rat metallothionein-I gene by sodium butyrate

Amplification of the metallothionein‐1 and metallothionein‐2 genes in copper‐resistant hepatoma cells

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