Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1993 Aug 1;293(Pt 3):807–812. doi: 10.1042/bj2930807

Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes.

Y Kamei 1, T Kawada 1, R Kazuki 1, E Sugimoto 1
PMCID: PMC1134439  PMID: 8394693

Abstract

Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. In the present study, the expression of retinoic acid receptors (RAR alpha, beta and gamma) and retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in rat adipose tissue and mouse 3T3-L1 adipose cells. The adipose tissue and/or 3T3-L1 cells expressed mRNAs for a number of nuclear retinoid receptors, including RAR alpha, beta and gamma, and RXR alpha, beta and gamma. RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs were abundant in adipose tissue and 3T3-L1 cells. RXR gamma mRNA was detected in adipose tissue but not in 3T3-L1 cells. Treatment of 3T3-L1 cells with 1 microM RA led to a 4-5-fold increase in the RAR gamma mRNA level, but only a trace amount of RAR beta mRNA was detected. RAR gamma mRNA expression was rapidly (within 2 h) induced by physiological concentrations of RA in a dose-dependent manner. The response of RAR gamma mRNA expression to RA was reversible; rapid disappearance of RAR gamma mRNA occurred on RA removal. In addition, the induction of RAR gamma expression did not require de novo protein synthesis, but was completely abolished by an inhibitor of RNA synthesis. Using RAR gamma 1 and gamma 2 isoform-specific probes, the patterns of RAR gamma 1 and gamma 2 mRNA expression in 3T3-L1 cells in the presence and absence of RA were examined. RAR gamma 1 mRNA was detected in 3T3-L1 cells but was not affected by RA treatment; however, RAR gamma 2 mRNA was strongly induced by RA.

Full text

PDF
807

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antras J., Lasnier F., Pairault J. Adipsin gene expression in 3T3-F442A adipocytes is posttranscriptionally down-regulated by retinoic acid. J Biol Chem. 1991 Jan 15;266(2):1157–1161. [PubMed] [Google Scholar]
  2. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  3. Bugge T. H., Pohl J., Lonnoy O., Stunnenberg H. G. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J. 1992 Apr;11(4):1409–1418. doi: 10.1002/j.1460-2075.1992.tb05186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies P. J., Murtaugh M. P., Moore W. T., Jr, Johnson G. S., Lucas D. Retinoic acid-induced expression of tissue transglutaminase in human promyelocytic leukemia (HL-60) cells. J Biol Chem. 1985 Apr 25;260(8):5166–5174. [PubMed] [Google Scholar]
  5. Dierich A., Gaub M. P., LePennec J. P., Astinotti D., Chambon P. Cell-specificity of the chicken ovalbumin and conalbumin promoters. EMBO J. 1987 Aug;6(8):2305–2312. doi: 10.1002/j.1460-2075.1987.tb02505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dowling J. E., Wald G. THE BIOLOGICAL FUNCTION OF VITAMIN A ACID. Proc Natl Acad Sci U S A. 1960 May;46(5):587–608. doi: 10.1073/pnas.46.5.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elder J. T., Fisher G. J., Zhang Q. Y., Eisen D., Krust A., Kastner P., Chambon P., Voorhees J. J. Retinoic acid receptor gene expression in human skin. J Invest Dermatol. 1991 Apr;96(4):425–433. doi: 10.1111/1523-1747.ep12469889. [DOI] [PubMed] [Google Scholar]
  8. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  9. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  10. Hamada K., Gleason S. L., Levi B. Z., Hirschfeld S., Appella E., Ozato K. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8289–8293. doi: 10.1073/pnas.86.21.8289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haq R., Chytil F. Expression of nuclear retinoic acid receptors in rat adipose tissue. Biochem Biophys Res Commun. 1991 May 15;176(3):1539–1544. doi: 10.1016/0006-291x(91)90462-g. [DOI] [PubMed] [Google Scholar]
  12. Hassouna N., Michot B., Bachellerie J. P. The complete nucleotide sequence of mouse 28S rRNA gene. Implications for the process of size increase of the large subunit rRNA in higher eukaryotes. Nucleic Acids Res. 1984 Apr 25;12(8):3563–3583. doi: 10.1093/nar/12.8.3563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heyman R. A., Mangelsdorf D. J., Dyck J. A., Stein R. B., Eichele G., Evans R. M., Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  14. Hoffmann B., Lehmann J. M., Zhang X. K., Hermann T., Husmann M., Graupner G., Pfahl M. A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter. Mol Endocrinol. 1990 Nov;4(11):1727–1736. doi: 10.1210/mend-4-11-1727. [DOI] [PubMed] [Google Scholar]
  15. Hu L., Gudas L. J. Cyclic AMP analogs and retinoic acid influence the expression of retinoic acid receptor alpha, beta, and gamma mRNAs in F9 teratocarcinoma cells. Mol Cell Biol. 1990 Jan;10(1):391–396. doi: 10.1128/mcb.10.1.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jump D. B., Bell A., Santiago V. Thyroid hormone and dietary carbohydrate interact to regulate rat liver S14 gene transcription and chromatin structure. J Biol Chem. 1990 Feb 25;265(6):3474–3478. [PubMed] [Google Scholar]
  17. Kamei Y., Kawada T., Fujita A., Etinne J., Noe L., Sugimoto E. Lipoprotein lipase enzyme expression in 3T3-L1 adipocytes is posttranscriptionally down-regulated by retinoic acid. Biochem Int. 1992 Apr;26(5):923–934. [PubMed] [Google Scholar]
  18. Kastner P., Krust A., Mendelsohn C., Garnier J. M., Zelent A., Leroy P., Staub A., Chambon P. Murine isoforms of retinoic acid receptor gamma with specific patterns of expression. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2700–2704. doi: 10.1073/pnas.87.7.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kato S., Mano H., Kumazawa T., Yoshizawa Y., Kojima R., Masushige S. Effect of retinoid status on alpha, beta and gamma retinoic acid receptor mRNA levels in various rat tissues. Biochem J. 1992 Sep 15;286(Pt 3):755–760. doi: 10.1042/bj2860755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kawada T., Aoki N., Kamei Y., Maeshige K., Nishiu S., Sugimoto E. Comparative investigation of vitamins and their analogues on terminal differentiation, from preadipocytes to adipocytes, of 3T3-L1 cells. Comp Biochem Physiol A Comp Physiol. 1990;96(2):323–326. doi: 10.1016/0300-9629(90)90699-s. [DOI] [PubMed] [Google Scholar]
  21. Kliewer S. A., Umesono K., Heyman R. A., Mangelsdorf D. J., Dyck J. A., Evans R. M. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1448–1452. doi: 10.1073/pnas.89.4.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kliewer S. A., Umesono K., Mangelsdorf D. J., Evans R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. doi: 10.1038/355446a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lehmann J. M., Zhang X. K., Pfahl M. RAR gamma 2 expression is regulated through a retinoic acid response element embedded in Sp1 sites. Mol Cell Biol. 1992 Jul;12(7):2976–2985. doi: 10.1128/mcb.12.7.2976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewski T., Chen J. Y., Staub A., Garnier J. M., Mader S. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992 Jan 24;68(2):377–395. doi: 10.1016/0092-8674(92)90478-u. [DOI] [PubMed] [Google Scholar]
  25. Leroy P., Krust A., Zelent A., Mendelsohn C., Garnier J. M., Kastner P., Dierich A., Chambon P. Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid. EMBO J. 1991 Jan;10(1):59–69. doi: 10.1002/j.1460-2075.1991.tb07921.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Leroy P., Nakshatri H., Chambon P. Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10138–10142. doi: 10.1073/pnas.88.22.10138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Levin A. A., Sturzenbecker L. J., Kazmer S., Bosakowski T., Huselton C., Allenby G., Speck J., Kratzeisen C., Rosenberger M., Lovey A. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992 Jan 23;355(6358):359–361. doi: 10.1038/355359a0. [DOI] [PubMed] [Google Scholar]
  28. Lowe J. B., Sacchettini J. C., Laposata M., McQuillan J. J., Gordon J. I. Expression of rat intestinal fatty acid-binding protein in Escherichia coli. Purification and comparison of ligand binding characteristics with that of Escherichia coli-derived rat liver fatty acid-binding protein. J Biol Chem. 1987 Apr 25;262(12):5931–5937. [PubMed] [Google Scholar]
  29. Mangelsdorf D. J., Borgmeyer U., Heyman R. A., Zhou J. Y., Ong E. S., Oro A. E., Kakizuka A., Evans R. M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992 Mar;6(3):329–344. doi: 10.1101/gad.6.3.329. [DOI] [PubMed] [Google Scholar]
  30. Mangelsdorf D. J., Ong E. S., Dyck J. A., Evans R. M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990 May 17;345(6272):224–229. doi: 10.1038/345224a0. [DOI] [PubMed] [Google Scholar]
  31. Mangelsdorf D. J., Umesono K., Kliewer S. A., Borgmeyer U., Ong E. S., Evans R. M. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell. 1991 Aug 9;66(3):555–561. doi: 10.1016/0092-8674(81)90018-0. [DOI] [PubMed] [Google Scholar]
  32. Marks M. S., Hallenbeck P. L., Nagata T., Segars J. H., Appella E., Nikodem V. M., Ozato K. H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J. 1992 Apr;11(4):1419–1435. doi: 10.1002/j.1460-2075.1992.tb05187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Martin C. A., Ziegler L. M., Napoli J. L. Retinoic acid, dibutyryl-cAMP, and differentiation affect the expression of retinoic acid receptors in F9 cells. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4804–4808. doi: 10.1073/pnas.87.12.4804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Morioka H., Tennyson G. E., Nikodem V. M. Structural and functional analysis of the rat malic enzyme gene promoter. Mol Cell Biol. 1988 Aug;8(8):3542–3545. doi: 10.1128/mcb.8.8.3542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Morré D. M. Intracellular actions of vitamin A. Int Rev Cytol. 1992;135:1–38. doi: 10.1016/s0074-7696(08)62037-9. [DOI] [PubMed] [Google Scholar]
  36. Négrel R., Grimaldi P., Ailhaud G. Establishment of preadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6054–6058. doi: 10.1073/pnas.75.12.6054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  38. Raynal F., Michot B., Bachellerie J. P. Complete nucleotide sequence of mouse 18 S rRNA gene: comparison with other available homologs. FEBS Lett. 1984 Feb 27;167(2):263–268. doi: 10.1016/0014-5793(84)80139-8. [DOI] [PubMed] [Google Scholar]
  39. Rees J. L., Daly A. K., Redfern C. P. Differential expression of the alpha and beta retinoic acid receptors in tissues of the rat. Biochem J. 1989 May 1;259(3):917–919. doi: 10.1042/bj2590917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Riaz-ul-Haq, Chytil F. Effect of retinoids on nuclear retinoic acid receptors mRNA in adipose tissue of retinol-deficient rats. J Lipid Res. 1992 Mar;33(3):381–384. [PubMed] [Google Scholar]
  41. Rottman J. N., Widom R. L., Nadal-Ginard B., Mahdavi V., Karathanasis S. K. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol. 1991 Jul;11(7):3814–3820. doi: 10.1128/mcb.11.7.3814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rubin C. S., Hirsch A., Fung C., Rosen O. M. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells. J Biol Chem. 1978 Oct 25;253(20):7570–7578. [PubMed] [Google Scholar]
  43. Singh G., Katyal S. L., Brown W. E., Kennedy A. L., Singh U., Wong-Chong M. L. Clara cell 10 kDa protein (CC10): comparison of structure and function to uteroglobin. Biochim Biophys Acta. 1990 Jul 6;1039(3):348–355. doi: 10.1016/0167-4838(90)90270-p. [DOI] [PubMed] [Google Scholar]
  44. Stone R. L., Bernlohr D. A. The molecular basis for inhibition of adipose conversion of murine 3T3-L1 cells by retinoic acid. Differentiation. 1990 Nov;45(2):119–127. doi: 10.1111/j.1432-0436.1990.tb00465.x. [DOI] [PubMed] [Google Scholar]
  45. Sucov H. M., Murakami K. K., Evans R. M. Characterization of an autoregulated response element in the mouse retinoic acid receptor type beta gene. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5392–5396. doi: 10.1073/pnas.87.14.5392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tsutsumi C., Okuno M., Tannous L., Piantedosi R., Allan M., Goodman D. S., Blaner W. S. Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem. 1992 Jan 25;267(3):1805–1810. [PubMed] [Google Scholar]
  47. Yu V. C., Delsert C., Andersen B., Holloway J. M., Devary O. V., När A. M., Kim S. Y., Boutin J. M., Glass C. K., Rosenfeld M. G. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. doi: 10.1016/0092-8674(91)90301-e. [DOI] [PubMed] [Google Scholar]
  48. Zelent A., Krust A., Petkovich M., Kastner P., Chambon P. Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature. 1989 Jun 29;339(6227):714–717. doi: 10.1038/339714a0. [DOI] [PubMed] [Google Scholar]
  49. Zelent A., Mendelsohn C., Kastner P., Krust A., Garnier J. M., Ruffenach F., Leroy P., Chambon P. Differentially expressed isoforms of the mouse retinoic acid receptor beta generated by usage of two promoters and alternative splicing. EMBO J. 1991 Jan;10(1):71–81. doi: 10.1002/j.1460-2075.1991.tb07922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zhang X. K., Hoffmann B., Tran P. B., Graupner G., Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature. 1992 Jan 30;355(6359):441–446. doi: 10.1038/355441a0. [DOI] [PubMed] [Google Scholar]
  51. Zovich D. C., Orologa A., Okuno M., Kong L. W., Talmage D. A., Piantedosi R., Goodman D. S., Blaner W. S. Differentiation-dependent expression of retinoid-binding proteins in BFC-1 beta adipocytes. J Biol Chem. 1992 Jul 15;267(20):13884–13889. [PubMed] [Google Scholar]
  52. de The H., Marchio A., Tiollais P., Dejean A. Differential expression and ligand regulation of the retinoic acid receptor alpha and beta genes. EMBO J. 1989 Feb;8(2):429–433. doi: 10.1002/j.1460-2075.1989.tb03394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. de Thé H., Vivanco-Ruiz M. M., Tiollais P., Stunnenberg H., Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177–180. doi: 10.1038/343177a0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES