Home LiteratureArticle Details
PMID: 8110186 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phorbol esters inhibit the glucocorticoid-mediated stimulation of cytosolic aspartate aminotransferase gene transcription.

The Biochemical journal ·Vol. 297 ( Pt 3) ·1994-02-01 ·Pages 497-502

Feilleux-Duché S, Garlatti M, Aggerbeck M, Bouguet J, Hanoune J, Barouki R

Abstract

The regulation of cytosolic aspartate aminotransferase (cAspAT) gene expression by phorbol esters was investigated in the highly differentiated hepatoma cell line Fao. Phorbol 12,13-dibutyrate (PdBu) had no effect on basal activity but partially inhibited the induction of cAspAT by dexamethasone. The extent of inhibition (40%) was similar to that obtained with insulin or vanadate. The inhibitory effects of PdBu and vanadate were additive. In the case of PdBu, the inhibitory effects could be eliminated by first incubating the cells with PdBu, which down-regulates protein kinase C. In contrast, inhibition by insulin was not modified by this treatment. The molecular mechanism of PdBu action was investigated. Northern blot analysis showed that the steady-state mRNA levels of cAspAT were decreased by PdBu in the presence of dexamethasone. In addition, the transcription rate, as measured by run-on experiments, was also decreased under the same conditions. Finally, a 2.4 kb promoter fragment driving the chloramphenicol acetyltransferase gene was stably transfected into the Fao cells. The regulation of the activity of this promoter fragment by dexamethasone and PdBu was similar to the regulation of the endogenous cAspAT activity. We conclude that PdBu acts by regulating the promoter activity of the cAsPAT gene.

MeSH Terms
Animals Aspartate Aminotransferases/genetics Cytosol/enzymology Dexamethasone/antagonists & inhibitors,pharmacology Isoenzymes/metabolism Phorbol 12,13-Dibutyrate/pharmacology Protein Kinase C/metabolism RNA, Messenger/metabolism Rats Transcription, Genetic/drug effects Tumor Cells, Cultured
Chemicals
Isoenzymes RNA, Messenger Phorbol 12,13-Dibutyrate Dexamethasone Aspartate Aminotransferases Protein Kinase C
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Feilleux-Duché S
INSERM U-99, Hôpital Henri Mondor, Créteil, France.
Garlatti M
Aggerbeck M
Bouguet J
Hanoune J
Barouki R
References (47)
47 references, click to expand
  1. The role of protein kinase C in cell surface signal transduction and tumour promotion.
    Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
  2. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection.
    Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81 PMID: 6294651
  3. Regulation of the urea cycle and TCA cycle by ammonia.
    Adv Enzyme Regul. 1966;4:317-36 PMID: 4229888
  4. Characterization of differentiated and dedifferentiated clones from a rat hepatoma.
    Biochimie. 1974;56(11-12):1603-11 PMID: 4157008
  5. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  6. Evidence for the participation of aspartate aminotransferase in hepatic glucose synthesis in the suckling newborn rat.
    Biochem J. 1978 Oct 15;176(1):335-8 PMID: 728114
  7. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells.
    Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6 PMID: 286319
  8. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  9. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.
    J Mol Appl Genet. 1982;1(4):327-41 PMID: 6286831
  10. Isolation of cDNA clones coding for rat tyrosine aminotransferase.
    Proc Natl Acad Sci U S A. 1982 Dec;79(23):7205-8 PMID: 6130522
  11. Characteristics of the desensitization and resensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells.
    Biochem J. 1982 Nov 15;208(2):317-22 PMID: 6297467
  12. Insulin-like effect of vanadate on adipocyte glycogen synthase and on phosphorylation of 95,000 dalton subunit of insulin receptor.
    Biochem Biophys Res Commun. 1983 May 31;113(1):80-6 PMID: 6407485
  13. Synergistic activation of rat hepatocyte glycogen phosphorylase by A23187 and phorbol ester.
    Biochem Biophys Res Commun. 1984 Feb 29;119(1):88-94 PMID: 6422939
  14. Cyclic AMP as a transcriptional inhibitor of upper eukaryotic gene transcription.
    Biochem Biophys Res Commun. 1984 Nov 30;125(1):135-41 PMID: 6095835
  15. Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7797-801 PMID: 6393128
  16. Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.
    Endocrinology. 1985 Jun;116(6):2650-5 PMID: 3158511
  17. Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. II. Identification of cAMP and glucocorticoid regulatory domains.
    J Biol Chem. 1986 Jul 25;261(21):9721-6 PMID: 3015903
  18. The effect of phorbol esters and diacylglycerol on expression of the phosphoenolpyruvate carboxykinase (GTP) gene in rat hepatoma H4IIE cells.
    J Biol Chem. 1986 Dec 25;261(36):16848-53 PMID: 3023368
  19. Separate enzymatic microassays for aspartate aminotransferase isoenzymes.
    Biochim Biophys Acta. 1987 Aug 13;925(2):175-84 PMID: 3620495
  20. Positive interaction between insulin and phorbol esters on the regulation of a specific messenger ribonucleic acid in rat hepatoma cells.
    Endocrinology. 1987 Oct;121(4):1227-32 PMID: 3308433
  21. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters.
    Nature. 1987 Oct 15-21;329(6140):648-51 PMID: 2821407
  22. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.
    Mol Cell Biol. 1987 Oct;7(10):3490-502 PMID: 3119989
  23. Insulin-glycerolipid mediators and gene expression.
    FASEB J. 1988 Jun;2(9):2453-61 PMID: 3286349
  24. Transcriptional regulation of a rat hepatoma gene by insulin and protein kinase-C.
    Endocrinology. 1988 Jul;123(1):366-72 PMID: 3289895
  25. Insulin action in normal and protein kinase C-deficient rat hepatoma cells. Effects on protein phosphorylation, protein kinase activities, and ornithine decarboxylase activities and messenger ribonucleic acid levels.
    Mol Endocrinol. 1987 Jan;1(1):44-52 PMID: 3331710
  26. The inhibition of phosphoenolpyruvate carboxykinase (guanosine triphosphate) gene expression by insulin is not mediated by protein kinase C.
    Mol Endocrinol. 1987 Jan;1(1):53-9 PMID: 3331712
  27. Rat cytosolic aspartate aminotransferase: regulation of its mRNA and contribution to gluconeogenesis.
    J Biochem. 1988 May;103(5):805-8 PMID: 3182750
  28. Nucleotide sequence and glucocorticoid regulation of the mRNAs for the isoenzymes of rat aspartate aminotransferase.
    J Biol Chem. 1988 Nov 25;263(33):17459-66 PMID: 3182856
  29. Inositol phosphates and cell signalling.
    Nature. 1989 Sep 21;341(6239):197-205 PMID: 2550825
  30. Regulation of cytosolic aspartate aminotransferase mRNAs in the Fao rat hepatoma cell line by dexamethasone, insulin and cyclic AMP.
    Eur J Biochem. 1989 Dec 8;186(1-2):79-85 PMID: 2557214
  31. Signaling through phosphatidylcholine breakdown.
    J Biol Chem. 1990 Jan 5;265(1):1-4 PMID: 2104616
  32. Hormonal discrimination among transcription start sites of aspartate aminotransferase.
    J Biol Chem. 1990 Mar 15;265(8):4444-8 PMID: 2307672
  33. The genes of hepatic glucose metabolism.
    J Biol Chem. 1990 Jun 25;265(18):10173-6 PMID: 2191945
  34. Analysis of dimerization and DNA binding functions in Fos and Jun by domain-swapping: involvement of residues outside the leucine zipper/basic region.
    Oncogene. 1990 Jun;5(6):929-39 PMID: 2113670
  35. Vanadate inhibits expression of the gene for phosphoenolpyruvate carboxykinase (GTP) in rat hepatoma cells.
    J Biol Chem. 1990 Aug 15;265(23):13677-82 PMID: 2166040
  36. Insulin stimulates the activity of a novel protein kinase C, PKC-epsilon, in cultured fetal chick neurons.
    J Biol Chem. 1990 Sep 5;265(25):15076-82 PMID: 2203768
  37. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone.
    Cell. 1990 Sep 21;62(6):1189-204 PMID: 2169351
  38. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction.
    Cell. 1990 Sep 21;62(6):1205-15 PMID: 2169352
  39. Metabolic effects of developmental, tissue-, and cell-specific expression of a chimeric phosphoenolpyruvate carboxykinase (GTP)/bovine growth hormone gene in transgenic mice.
    J Biol Chem. 1990 Dec 25;265(36):22371-9 PMID: 1702419
  40. Adipsin gene expression in 3T3-F442A adipocytes is posttranscriptionally down-regulated by retinoic acid.
    J Biol Chem. 1991 Jan 15;266(2):1157-61 PMID: 1985940
  41. Regulation of gene expression by tumor promoters.
    Pharmacol Ther. 1990;48(2):157-88 PMID: 2293238
  42. Signal transduction convergence: phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence.
    Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6580-4 PMID: 1650476
  43. Effects of phorbol esters on insulin receptor function and insulin action in hepatocytes: evidence for heterogeneity.
    Mol Cell Biochem. 1992 Feb 12;109(2):115-8 PMID: 1625677
  44. Differential down-regulation of insulin-sensitive protein kinase-C isoforms by 12-O-tetradecanoylphorbol-13-acetate in rat adipocytes and BC3H-1 myocytes.
    Endocrinology. 1993 Feb;132(2):689-92 PMID: 8425487
  45. Protein kinase C isoenzymes: divergence in signal transduction?
    Biochem J. 1993 Apr 15;291 ( Pt 2):329-43 PMID: 8484714
  46. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  47. Stimulation of hepatic glycogenolysis by 12-O-tetradecanoylphorbol-13-acetate (TPA) via a calcium requiring process.
    Biochem Biophys Res Commun. 1984 Aug 16;122(3):1057-64 PMID: 6089774
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2970497
Published
1994-02-01
Pages
497-502
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1137861
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2970497 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2