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Modulation of gene expression by vitamin B6

Published online by Cambridge University Press:  14 December 2007

T. Oka
T. Oka*
Affiliation:
Department of Veterinary Physiology, Faculty of Agriculture, Kagoshima University1-21-24 Korimoto, Kagoshima 890-0065, Japan
*
Corresponding author: Professor T. Oka, fax +81 99 285 8714, email oka@vet.agri.kagoshima-u.ac.jp
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Abstract

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The physiologically active form of vitamin B6, pyridoxal 5′-phosphate (PLP), is known to function as a cofactor in many enzymic reactions in amino acid metabolism. Recent studies have shown that, apart from its role as a coenzyme, PLP acts as a modulator of steroid hormone receptor-mediated gene expression. Specifically, elevation of intracellular PLP leads to a decreased transcriptional response to glucocorticoid hormones, progesterone, androgens, and oestrogens. For example, the induction of cytosolic aspartate aminotransferase (cAspAT) in rat liver by hydrocortisone is suppressed by the administration of pyridoxine. The suppression of the cAspAT induction by pyridoxine is caused by a decrease in the expression of the cAspAT gene, which is brought about by inactivation of the binding activity of the glucocorticoid receptor to the glucocorticoid-responsive element in the regulatory region of the cAspAT gene. Vitamin B6 has recently been found to modulate gene expression not only for steroid hormone-responsive or PLP-dependent enzymes but also for steroid- and PLP-unrelated proteins such as serum albumin. Albumin gene expression was found to be modulated by vitamin B6 through a novel mechanism that involves inactivation of tissue-specific transcription factors, such as HNF-1 or C/EBP, by direct interaction with PLP in a similar manner to glucocorticoid receptor. Enhancement of albumin gene expression in the liver by an increased supply of amino acids can be explained by elevated binding of HNF-1 and C/EBP to their DNA-binding sites which, in turn, is caused by a decrease in the intracellular level of PLP by the increased amino acid supply. These findings that vitamin B6 acts as a physiological modulator of gene expression add a new dimension to the hitherto recognized function of vitamin B6 as a cofactor of enzyme action.

Keywords

Vitamin B6Gene expressionTranscription factorsSteroid hormonesAlbuminCancer
Type
Research Article
Information
Nutrition Research Reviews , Volume 14 , Issue 2 , December 2001 , pp. 257 - 266
Copyright
Copyright © CABI Publishing 2001

References

Allgood, VE & Cidlowski, JA(1992) Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily. Journal of Biological Chemistry 267, 3819–3824.CrossRefGoogle ScholarPubMed
Allgood, VE, Oakley, RH & Cidlowski, JA(1993) Modulation by vitamin B6 of glucocorticoid receptor-mediated gene expression requires transcription factors in addition to the glucocorticoid receptor. Journal of Biological Chemistry 268, 20870–20876.CrossRefGoogle Scholar
Allgood, VE, Powell-Oliver, FE & Cidlowski, JA (1990) Vitamin B6 influences glucocorticoid receptor-dependent gene expression. Journal of Biological Chemistry 265, 12424–12433.CrossRefGoogle ScholarPubMed
Basu, A, Tirumalai, RS & Modak, MJ(1989) Substrate binding in human immunodeficiency virus reverse transcriptase. Journal of Biological Chemistry 264, 8746–8752.CrossRefGoogle ScholarPubMed
Bender, DA (1987) Oestrogens and vitamin B6 – actions and interactions. World Review of Nutrition and Dietetics 51, 140–189.CrossRefGoogle Scholar
Bender, DA (1994) Novel functions of vitamin B6. Proceedings of the Nutrition Society 53, 625–630.CrossRefGoogle ScholarPubMed
Cake, MH, DiSorbo, DM & Litwack, G(1978) Effect of pyridoxal phosphate on the DNA binding site of activated hepatic glucocorticoid receptor. Journal of Biological Chemistry 253, 4886–4891.CrossRefGoogle ScholarPubMed
Cereghini, S, Raymondjean, M, Carranca, AG, Herbomel, P & Yaniv, M (1987) Factors involved in control of tissue-specific expression of albumin gene. Cell 50, 627–638.CrossRefGoogle ScholarPubMed
Chang, SJ, Chuang, HJ & Chen, HH (1999) Vitamin B6 down-regulates the expression of human GPIIb gene. Journal of Nutritional Science and Vitaminology 45, 471–479.CrossRefGoogle ScholarPubMed
Chang, SJ & Mak, OT (1999) The optimal levels of vitamin B6 in platelet function and blood coagulation of rabbits. Nutrition Research 19, 65–73.CrossRefGoogle Scholar
Chiku, K, Mochida, H, Yamamoto, M & Natori, Y (1993) Amino acids suppress intracellular protein degradation in rat liver during parenteral nutrition. Journal of Nutrition 123, 1771–1776.CrossRefGoogle ScholarPubMed
Chrisley, BM & Hendricks, TS (1986) Vitamin B6 status of a group of cancer patients. Nutrition Research 6, 1023–1029.CrossRefGoogle Scholar
Diffley, JFX (1988) Affinity labeling the DNA polymerase a complex. 1. Pyridoxal 5′-phosphate inhibition of DNA polymerase a complex from Drosophila melanogaster embryos. Journal of Biological Chemistry 263, 14669–14677.CrossRefGoogle Scholar
DiSorbo, DM & Litwack, G (1981) Changes in the intracellular levels of pyridoxal 5′-phosphate affect the induction of tyrosine aminotransferase by glucocorticoid. Biochemical and Biophysical Research Communications 99, 1203–1208.CrossRefGoogle Scholar
DiSorbo, DM & Litwack, G (1982) Vitamin B6 kills hepatoma cells in culture. Nutrition and Cancer 3, 216–222.CrossRefGoogle ScholarPubMed
DiSorbo, DM & Nathanson, L (1983) High-dose pyridoxal supplemented culture medium inhibits the growth of a human malignant myeloma cell line. Nutrition and Cancer 5, 10–15.CrossRefGoogle Scholar
Dragunow, M & Robertson, HA (1987) Kindling stimulation induced c-fos protein(s) in granule cells of the rat dendate gyrus. Nature (London) 329, 441–442.CrossRefGoogle Scholar
Dragunow, M & Robertson, HA (1988) Brain injury induced c-fos protein(s) in nerve and glia-like cells in adult mammalian brain. Brain Research 455, 295–299.CrossRefGoogle Scholar
Fisher, EH, Kent, AB, Snyder, ER & Krebs, EG (1958) The reaction of sodium borohydrate with muscle phosphorylase. Journal of the American Chemical Society 80, 2906–2907.CrossRefGoogle Scholar
Kloczowia, KM & Freinberg, H (1980) Pyridoxal phosphate inhibition on platelet function. American Journal of Physiology 238, H54–H60.Google Scholar
Komatsu, S, Watanabe, H, Oka, T, Tsuge, H, Nii, H & Kato, N (2001) Supplemental vitamin B6 suppresses azoxymethane-induced colon tumorgenesis in mice by reducing cell proliferation. Journal of Nutrition 131, 2204–2207.CrossRefGoogle Scholar
Kondo, T & Okada, M (1985) Effect of pyridoxine administration on the induction of cytosolic aspartate aminotransferase in the liver of rats treated with hydrocortisone. Journal of Nutritional Science and Vitaminology 31, 509–517.CrossRefGoogle ScholarPubMed
Majumder, PK, Joshi, JB & Banerjee, MR (1983) Correlation between nuclear glucocorticoid receptor levels and casein gene expression in murine mammary gland in vitro. Journal of Biological Chemistry 258, 6793–6798.CrossRefGoogle ScholarPubMed
Makino, K & Matsuda, M (1960) Vitamin B6 enzymes and convulsion. Shinkei Kenkyu no Shimpo (Japanese) 4, 72–76.Google Scholar
Marie, P, Wuarin, J & Shibler, U (1989) The role of cis-acting promoter elements in tissue-specific albumin gene expression in rat liver. Science 244, 343–346.CrossRefGoogle Scholar
Martial, L, Zardivar, J, Bull, P, Venegas, A & Valenzuela, P (1975) Inactivation of rat liver RNA polymerase I and II and yeast RNA polymerase I by pyridoxal 5′-phosphate. Evidence for the participation of lysyl residue at the active site. Biochemistry 14, 4907–4911.CrossRefGoogle ScholarPubMed
Merrill, AH & Henderson, JM (1987) Disease associated with deficiencies in vitamin B6 metabolism or utilization. Annual Review of Nutrition 7, 137–156.CrossRefGoogle ScholarPubMed
Merrill, AH, Henderson, JM, Wang, E, McDonald, BW & Millikan, WJ (1984) Metabolism of vitamin B6 by human liver. Journal of Nutrition 114, 1664–1674.CrossRefGoogle ScholarPubMed
Mizuno, AM, Mizobuchi, T, Ishibashi, Y & Matsuda, M (1989) c-Fos mRNA induction under vitamin B6 antagonist-induced seizure. Neuroscience Letters 98, 272–275.CrossRefGoogle ScholarPubMed
Modak, MJ (1976) Observation on the pyridoxal 5′-phosphate inhibition of DNA polymerases. Biochemistry 15, 3620–3626.CrossRefGoogle ScholarPubMed
Molina, A, Oka, T, Munoz, S, Chikamori-Aoyama, M, Kuwahata, M & Natori, Y (1997) Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma cell line HepG2. Nutrition and Cancer 28, 206–211.CrossRefGoogle Scholar
Morgan, JI, Cohen, DR, Hempstead, JL & Curran, T (1987) Mapping pattern of c-fos expression in the central nervous system after seizure. Science 237, 192–197.CrossRefGoogle ScholarPubMed
Nishigori, H, Moudgli, VK & Toft, D (1978) Inactivation of avian progesterone receptor binding to ATP-sepharose by pyridoxal 5′-phosphate. Biochemical and Biophysical Research Communications 80, 112–118.CrossRefGoogle ScholarPubMed
Nurden, AT & Phillip, DR (1990) Platelet membrane glycoproteins: functions in cellular interactions. Annual Review of Cell Biology 6, 329–357.Google Scholar
Oka, T, Komori, N, Kuwahata, M, Hiroi, Y, Shimoda, T, Okada, M & Natori, Y (1995 a) Pyridoxal 5'-phosphate modulates expression of cytosolic asparate aminotransferase gene by inactivation of glucocorticoid receptor. Journal of Nutritional Science and Vitaminology 41, 363–375.CrossRefGoogle Scholar
Oka, T, Komori, N, Kuwahata, M, Okada, M & Natori, Y (1995 b) Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver. Biochemical Journal 309, 242–248.CrossRefGoogle ScholarPubMed
Oka, T, Komori, N, Kuwahata, M, Sassa, T, Suzuki, I, Okada, M & Natori, Y (1993) Vitamin B6 deficiency causes activation of RNA polymerase and general enhancement of gene expression in rat liver. FEBS Letters 331, 162–164.CrossRefGoogle ScholarPubMed
Oka, T, Komori, N, Kuwahata, M, Suzuki, I, Okada, M & Natori, Y (1994) Effect of vitamin B6 deficiency on the expression of glycogen phosphorylase mRNA in rat liver and skeletal muscle. Experientia 50, 127–129.CrossRefGoogle ScholarPubMed
Oka, T, Kuwahata, M, Sugitatsu, H, Tsuge, H, Asagi, K, Kohri, H, Horiuchi, S & Natori, Y (1997) Modulation of albumin gene expression by amino acid supply in rat liver is mediated through intracellular concentration of pyridoxal 5′-phosphate. Journal of Nutritional Biochemistry 8, 211–216.CrossRefGoogle Scholar
Potera, C, Rose, DP & Brown, RR (1977) Vitamin B6 deficiency in cancer patients. American Journal of Clinical Nutrition 30, 1677–1679.CrossRefGoogle ScholarPubMed
Tryfiates, GP (1980) Vitamin B6: Metabolism and Role in Growth. Westport, CT: Food and Nutrition Press.Google Scholar
Tully, DB, Allgood, VE & Cidlowski, JA (1994) Modulation of steroid receptor-mediated gene expression by vitamin B6. FASEB Journal 8, 343–349.CrossRefGoogle ScholarPubMed
Venegas, A, Martial, J & Valenzuela, P (1973) Active site-directed inhibition of E. coli DNA-dependent RNA polymerase by pyridoxal 5′-phosphate. Biochemical and Biophysical Research Communications 55. 1053–1059.CrossRefGoogle ScholarPubMed
Verstraete, M & Zoldhelyi, P (1995) Novel antithromboric drugs in development. Drugs 49, 856–884.CrossRefGoogle ScholarPubMed