Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids

Hager, Lisa J.; Palmiter, Richard D.

doi:10.1038/291340a0

Cited by 273 publications

(105 citation statements)

References 26 publications

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“…It is also interesting that there is a growing body of evidence indicating structural homology between the receptor which mediates induction by 3-methylcholanthrene and the glucocorticoid receptor [47]. Our studies further substantiate this possibility in that 3-methylcholanthrene induced several acute-phase proteins, some of which are also known to be regulated by glucocorticoids [48]. The exact mechanism and implications of the regulation of these genes by foreign compounds remains to be clarified.…”

Section: Northern Blot Analysis Of Cytochrome P-450 and Acute-phase Msupporting

confidence: 74%

Potentiation and suppression of mouse liver cytochrome P‐450 isozymes during the acute‐phase response induced by bacterial endotoxin

Stanley

Adams

Lindsay

et al. 1988

European Journal of Biochemistry

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Infection and inflammation are known to affect the metabolism and disposition of drugs and carcinogens. We report a detailed study of the effects of bacterial endotoxin on the constitutive and inducible expression and activities of cytochrome P-450 isozymes from families P-4501, P-450IIB, P-45OIIC and P-450111. In general high doses of high endotoxin caused very marked suppression of P-450 isozymes and associated activities. However, this effect was differential, the expression of certain isozymes being only slightly reduced whereas others were suppressed to almost undetectable levels. Low doses of endotoxin also gave differential effects on cytochrome P-450 expression. Of particular interest was the very marked potentiation of the inductive effect of both 3-methylcholanthrene and phenobarbital. In the case of 3-methylcholanthrene the 10-fold induction of activity was increased to 24-fold by concomitant endotoxin administration. In this regard it was interesting that 3-methylcholanthrene was an effective inducer of a wide variety of acute-phase proteins including metallothionein, serum amyloid A, fibrinogen and hemopexin.These data show that endotoxin, and therefore bacterial infection and inflammation, can have profound and differential effects on components of the cytochrome-P-450 monooxygenase system which could result in significant changes in susceptibility to the effects of drugs, chemical toxins and carcinogens.

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Section: Northern Blot Analysis Of Cytochrome P-450 and Acute-phase Msupporting

confidence: 74%

Potentiation and suppression of mouse liver cytochrome P‐450 isozymes during the acute‐phase response induced by bacterial endotoxin

Stanley

Adams

Lindsay

et al. 1988

European Journal of Biochemistry

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“…MT gene expression is predominantly regulated at the level of transcription [5][6][7][8][9]. Though the mechanism of regulation is poorly understood, rapid induction occurs upon exposure to metals [5] and, in mammalian cells, to various circulating factors such as glucocorticoid hormones [6], ainterferon [7], and interleukin-1 and other mediators of the inflammatory response [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Though the mechanism of regulation is poorly understood, rapid induction occurs upon exposure to metals [5] and, in mammalian cells, to various circulating factors such as glucocorticoid hormones [6], ainterferon [7], and interleukin-1 and other mediators of the inflammatory response [8,9]. It has been suggested that a common pathway for MT induction involves protein kinase C (PKC) activation since MT levels increase in serum-starved cells after treatment with growth factors and TPA, agents which function in part through PKC activation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Metallothionein RNA levels in HL‐60 cells Effect of cadmium, differentiation, and protein kinase C activation

1988

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Metallothionein (MT) gene transcription is regulated in a developmental and tissue-specific manner by metal ions and other agents. We examined MT expression in the human promyelocytic leukemia cell line HL-60 during differentiation along macrophage and neutrophil lineages. All HL-60 phenotypes showed similar basal levels of MT RNA with significant induction following exposure to Cd 2+ but not activators of PKC. MT RNA did not correlate with growth state or with known levels of PKC activity, thus our data do not support a role for MT in HL-60 differentiation or for PKC in MT expression.

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“…In an effort to increase the expression of transfected globin genes, we used mammalian inducible promoters such as the mouse metallothionein (MT-I) gene to enhance human globin gene transcription. In an experiment involving a hybrid gene (MaG) that contains the 5' promoter-regulator sequence of the mouse MT-I gene and the coding sequences of the human a-globin gene, we showed that the transcription of this hybrid gene could be regulated with inducer molecules such as cadmium (12,14,31). However, the amount of mRNA produced was still insufficient to support adequate globin translation (Y.-F. Lau et al, manuscript in preparation).…”

mentioning

confidence: 99%

Amplification and expression of human alpha-globin genes in Chinese hamster ovary cells.

Lau¹,

Lin²,

Kan³

1984

Mol. Cell. Biol.

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We studied the effects of gene amplification on human globin gene expression in Chinese hamster ovary cells. The normal human a-globin gene (Na2) and a hybrid gene (MaG) containing the 5' promoter-regulator region of the mouse metallothionein gene and the human structural aL2-globin gene were linked to a modular SV2-cDNA dihydrofolate reductase (DHFR) gene. The recombinant DNA molecules were introduced into Chinese hamster ovary cells by calcium phosphate precipitation. After initial selection to retain the DHFR and linked sequences, the cells were cultured in increasing concentrations of methotrexate up to 0.2 mM. Southern blot analysis of total cellular DNA showed an approximately 500-to 1,000-fold increase in the number of copies of DHFR and human ot-globin genes. The transcription of the a-globin and DHFR genes increased as their copy number within the cells increased. The transcription of the amplified hybrid MaG gene was also inducible with cadmium treatments. Both mature mRNA and "read-through" transcripts were observed. DHFR constituted approximately 10% of pulse-labeled cellular proteins in these cells, but no human a-globin was detected. In vitro translation of polyadenylated RNA from these cells showed that a-globin mRNA transcribed from the amplified a-globin genes was functional and directed a-globin chain synthesis. In situ hybridization of 3H-labeled oa-globin and DHFR DNA probes in chromosome preparations from the two cell lines indicated that both genes were coamplified in the same chromosomal locations in each cell type. These results indicate that gene amplification enhances human globin gene expression in cultured Chinese hamster ovary cells.

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Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids

Cited by 273 publications

References 26 publications

Potentiation and suppression of mouse liver cytochrome P‐450 isozymes during the acute‐phase response induced by bacterial endotoxin

Potentiation and suppression of mouse liver cytochrome P‐450 isozymes during the acute‐phase response induced by bacterial endotoxin

Metallothionein RNA levels in HL‐60 cells Effect of cadmium, differentiation, and protein kinase C activation

Amplification and expression of human alpha-globin genes in Chinese hamster ovary cells.

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