Induction of glutathione S-transferase by phenobarbital in rat hepatocyte culture.

Sasaki, Haruyo; Miyaura, Shuichi; Horie, Kiyoko; Isono, Hideo

doi:10.1248/bpb1978.12.775

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…The modulation of AGP gene expression by phenobarbital in vitro was obtained with the same concentrations used in similar models to induce drug-and steroidmetabolizing enzymes, mainly cytochrome P-450 I1 B (30)(31)(32) and GST (33). However, whereas transcriptional activation of the cytochrome P-450 IIB gene was detected only a few hours after a single administration of PB, induction of GST required several days of regular phenobarbital treatment.…”

Section: Discussionmentioning

confidence: 92%

Phenobarbital induction of α1-acid glycoprotein in primary rat hepatocyte cultures

et al. 1994

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The serum level of rat alpha 1-acid glycoprotein is significantly increased by treatment with phenobarbital, and in vivo studies have shown that phenobarbital seems to act mainly at the transcriptional level. To show the direct mediating effect of phenobarbital on alpha 1-acid glycoprotein gene expression, we investigated the ability of primary cultured rat hepatocytes to respond to in vitro phenobarbital administration. Phenobarbital increased both alpha 1 acid glycoprotein secretion and corresponding mRNA levels in primary rat hepatocytes cultured on matrigel. Used in combination with interleukin-1, interleukin-6 and dexamethasone, phenobarbital had an additive or synergistic effect on alpha 1-acid glycoprotein synthesis. These results show that (a) phenobarbital acts directly on hepatocytes by increasing alpha 1-acid glycoprotein gene expression and (b) this effect is mediated by a specific mechanism independent of pathways involved in alpha 1-acid glycoprotein induction by interleukin-1, interleukin-6 and glucocorticoids.

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Section: Discussionmentioning

confidence: 92%

Phenobarbital induction of α1-acid glycoprotein in primary rat hepatocyte cultures

et al. 1994

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“…Previous studies have demonstrated that treatment with PB, in vivo [11,32] or in vitro [22], increases rat liver GST enzymatic activity. The increase in vivo is caused by an increased amount of GST proteins 1 and 106 3 especially [ll], which is a result of an increased translational activity [13].…”

Section: Discussionmentioning

confidence: 99%

Regulation of glutathione S‐transferase gene expression by phenobarbital in cultured adult rat hepatocytes

et al. 1991

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Previous studies, by using Northern blotting analyses, showed that phenobarbital (PB) affects the steady-state mRNA levels of glutathione S-transferase (GST) subunits l/2, 314 and 7 in both conventional cultures of adult rat hepatocytes and cotuttures, with rat liver epithelial cells [Vandenberghe ct al., 1989, FEW Lett. 2.51, 59-64;Morel et al., 1989, FEBS Lett. 258, 99-1021. To determine whether PB acts at the transcriptional level, nuclear 'run-on' experiments using cDNA probes hybridizing to GST subunits l/2, 3/4 and 7 mRNA were performed on purified nuclei isolated from control and PI3 treated hepatocytes seeded under conventional and co-culture conditions. Data from this study demonstrate that the increase in steady-state mRNA levels observed in both conventionai cuIture and co-culture after 4 days PB exposure results from an increased tmns~ptional activity of the GST genes. However, a substantial increase in steady-state mRNA levels in the absence of a commensurate increase in transcriptional activity at 12 days of co-culture, indicates that the barbiturate has also a skbilizing effect in vitro on the GST mRNAs.Glutathione S-transferase; Gene transcription; Rat hepatocyte; Primary culture; Phenobarbital 1, INTRODUCTIONPhenobarbital (PB) has previously been reported to alter the expression, regulation and activity of several liver drug metabolizing enzymes [l-3]. Most attention has been paid to its effect on cytochrome P-450 [4-61, UDP-glucuronyltransferase [7,8] and glutathione Stransferase enzymes [9-l 11, However, it is yet not clear how this compound affects the regulation of expression of these enzymes. It is not known whether PB induction of transcriptional and translational activities involves one or more receptors [12,13].It has been shown that PB does not elevate alf cytochrome P-450 enzymes to the same extent. Cytochrome P-450 IIBI and III32 are the major liver enzymes to be induced [ 14,151. The rapid increase in the rates of transcription and the appearance of elevated Ievels of nuclear pre-mRNA and cytoplasmi~ mRNAs unequivocaily demonstrated that PB elevates levels of cytochrome P-450 III& and IIBz primarily by augmenting th: rate of transcription of the respective genes Rat bcpatocytes were isolated from Sprague-Dawley rats (ISO-ZOO 11, 1348 Mont-St-Guibert, Belgium. Fax: (32) (10) 450290. g) as described by Gugucn et al. [23). I'hcy were sccdcd in convcnm result from an increased transcriptional activity as found for the intact liver. Liver glutathione ~-transferase subunits 1 and 3 especially are also induced by PB treatment Ill]. Recently, Pickett et al. [20] reported that the increase of GST mRNA in total liver after PB addition results from an elevated GST gene transcription. In cultured hepatocytes, PB treatment induces the GST enzymatic activity 121,223. It was shown in previous study [21] that, by supplementing the culture medium with 3.2 mM PB, concentrations of individual GST subunits and GST steady-state mRNA levels were changed. However, no information is available on the re...

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“…In Anopheles gambiae, GSTs play an important role in conferring insecticide resistance (Ding et al, 2003). Additionally, glutathione S-transferases have also been shown to be PB inducible in both insects and mammals (Sasaki et al, 1989;Pinkus et al, 1993;Tang & Tu, 1995).…”

Section: Figure 1 Fold Induction Of Genes In Third Instars Treated Wmentioning

confidence: 99%

Genome‐wide analysis of phenobarbital‐inducible genes in Drosophila melanogaster

Sun

Margam

Sun

et al. 2006

Insect Molecular Biology

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An oligoarray analysis was conducted to determine the differential expression of genes due to phenobarbital exposure in Drosophila melanogaster (w(1118) strain) third instar larvae. Seventeen genes were observed to be induced with increased expression by a statistical analysis of microarrays approach with a q < or = 0.05. At q < or = 0.12, four more genes (Cyp12d1, DmGstd4, and two genes with unknown function) were found to be up-regulated, and 11 genes with unknown function were found to be down-regulated. Fifteen of these genes, Cyp4d14, Cyp6a2, Cyp6a8, Cyp12d1, Cyp6d5, Cyp6w1, CG2065, DmGstd6, DmGstd7, Amy-p/Amy-d, Ugt86Dd, GC5724, Jheh1, Jheh2 and CG11893, were verified using quantitative real time polymerase chain reaction. Some of these genes have been shown to be over-transcribed in metabolically DDT-resistant Drosophila strains.

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Induction of glutathione S-transferase by phenobarbital in rat hepatocyte culture.

Cited by 8 publications

References 13 publications

Phenobarbital induction of α1-acid glycoprotein in primary rat hepatocyte cultures

Phenobarbital induction of α1-acid glycoprotein in primary rat hepatocyte cultures

Regulation of glutathione S‐transferase gene expression by phenobarbital in cultured adult rat hepatocytes

Genome‐wide analysis of phenobarbital‐inducible genes in Drosophila melanogaster

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