Skip to main content
SpringerLink
Log in

Corticoadrenal activity regulates in rat betaine-homocysteine S-methyltransferase expression with opposites effects in liver and kidney

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Betaine-homocysteine S-methyltransferase (BHMT) is an enzyme that converts homocysteine (Hcy) to methionine using betaine as a methyl donor. Betaine also acts as osmolyte in kidney medulla, protecting cells from high extracellular osmolarity. Hepatic BHMT expression is regulated by salt intake. Hormones, particularly corticosteroids, also regulate BHMT expression in rat liver. We investigated to know whether the corticoadrenal activity plays a role in kidney BHMT expression. BHMT activity in rat kidneys is several orders of magnitude lower than in rat livers and only restricted to the renal cortex. This study confirms that corticosteroids stimulate BHMT activity in the liver and, for the first time in an animal model, also up-regulate the BHMT gene expression. Besides, unlike the liver, corticosteroids in rat kidney down-regulate BHMT expression and activity. Given that the classical effect of adrenocortical activity on the kidney is associated with sodium and water re-absorption by the distal tubule leading to volume expansion, by promoting lesser use of betaine as a methyl donor, corticosteroids would preserve betaine for its other role as osmoprotectant against changes in the extracellular osmotic conditions. We conclude that corticosteroids are, at least in part, responsible for the inhibition of BHMT expression and activity in rat kidneys.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Adachi H, Hirai Y, Fujiura Y, Matsuoka H, Satoh A and Imaizumi T 2002 Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Stroke 33 2177–2181

    Article  PubMed  CAS  Google Scholar 

  • Albert CM, Rifai N, Stampfer MJ and Ridker PM 2002 Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 105 2595–2599

    Article  PubMed  CAS  Google Scholar 

  • Ali R, Amlal H, Burnham CE and Soleimani M 2000 Glucocorticoids enhance the expression of the basolateral Na+:HCO3− cotransporter in renal proximal tubules. Kidney Int. 57 1063–1071

    Article  PubMed  CAS  Google Scholar 

  • Bagnasco S, Balaban R, Fales HM, Yang YM and Burg M 1986 Predominant osmotically active organic solutes in rat and rabbit renal medullas. J. Biol. Chem. 261 5872–5877

    PubMed  CAS  Google Scholar 

  • Bailey MA, Mullins JJ and Kenyon CJ 2009 Mineralocorticoid and glucocorticoid receptors stimulate epithelium channel activity in a mouse model of Cushing syndrome. Hypertension 54 890–896

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM 1972 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72 248–254

    Article  Google Scholar 

  • Bruno A, Carucci P, Cassader M, Cavallo-Perin P, Gruden G, Olivetti C and Pagano G 1994 Serum glucose, insulin and C-peptide response to oral glucose after intravenous administration of hydrocortisone and methylprednisolone in man. Eur. J. Clin. Pharmacol. 46 411–415

    Article  PubMed  CAS  Google Scholar 

  • Chen LH, Liu ML, Hwang HY, Chen LS, Korenberg J and Shane B 1997 Human methionine synthase. cDNA cloning, gene localization, and expression. J. Biol. Chem. 272 3628–3634

    Article  PubMed  CAS  Google Scholar 

  • De Zwart FJ, Slow S, Payne RJ, Lever M, George PM, Gerrard JA and Chambers ST 2003 Glycine betaine and glycine betaine analogues in common foods. Food Chem. 83 197–204

  • Delgado-Reyes CV and Garrow TA 2005 High sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression in guinea pig liver and kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288 R182–R187

    Article  PubMed  CAS  Google Scholar 

  • Delgado-Reyes CV, Wallig MA and Garrow TA 2001 Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney. Arch. Biochem. Biophys. 393 184–186

    Article  PubMed  CAS  Google Scholar 

  • Duerre JA and Miller CH 1966 Preparation of L-homocysteine from L-homocysteine thiolactone. Anal. Biochem. 17 310–315

    Article  CAS  Google Scholar 

  • Finkelstein JD, Harris BJ, Martin JJ and Kyle WE 1982 Regulation of hepatic betaine-homocysteine methyltransferase by dietary methionine. Biochem. Biophys. Res. Commun. 108 344–348

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein JD, Kyle WE and Harris BJ 1971 Methionine metabolism in mammals. Regulation of homocysteine methyltransferases in rat tissue. Arch. Biochem. Biophys. 146 84–92

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein JD and Martin JJ 1986 Methionine metabolism in mammals. Adaptation to methionine excess. J. Biol. Chem. 261 1582–1587

    PubMed  CAS  Google Scholar 

  • Finkelstein JD and Mudd SH 1967 Trans-sulfuration in Mammals. The methionine sparing effect of cysteine. J. Biol. Chem. 242 873–880

    PubMed  CAS  Google Scholar 

  • Fischer LM, Scearce JA, Mar M-H, Patel JR, Blanchard RT, Macintosh BA, Busby MG and Zeisel SH 2005 Ad libitum choline intake in healthy individuals meets or exceeds the proposed adequate intake level. J. Nutr. 135 826–829

    PubMed  CAS  Google Scholar 

  • Gaeggeler HP, Gonzalez-Rodriguez E, Jaeger NF, Loffing-Cueni D, Norregaard R, Loffing J, Horisberger JD and Rossier BC 2005 Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosterone-stimulated sodium transport in a novel renal cell line. J. Am. Soc. Nephrol. 16 878–891

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Perez A and Burg MB 1991 Renal medullary osmolytes. Physiol. Rev. 71 1081–1115

    PubMed  CAS  Google Scholar 

  • Garrow TA 1996 Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase. J. Biol. Chem. 271 22831–22838

    PubMed  CAS  Google Scholar 

  • Häussinger D 1996 The role of cellular hydration in the regulation of cell function. Biochem. J. 313 697–710

    PubMed  Google Scholar 

  • Mangos GJ, Turner SW, Fraser TB and Whitworth JA 2000 The role of corticosterone in corticotrophin (ACTH)-induced hypertension in the rat. J. Hypertens. 18 1849–1855

    Article  PubMed  CAS  Google Scholar 

  • McKeever MP, Weir DG, Molloy A and Scott JM 1991 Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat. Clin. Sci. 81 551–556

    PubMed  CAS  Google Scholar 

  • Millian NS and Garrow TA 1998 Human betaine-homocysteine methyltransferase is a zinc metalloenzyme. Arch. Biochem. Biophys. 356 93–98

    Article  PubMed  CAS  Google Scholar 

  • Ortiz PA and Garvin JL 2001 Intrarenal transport and vasoactive substances in hypertension. Hypertension 38 621–624

    Article  PubMed  CAS  Google Scholar 

  • Park EI and Garrow TA 1999 Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene. J. Biol. Chem. 274 7816–7824

    Article  PubMed  CAS  Google Scholar 

  • Park EI, Renduchintala MS and Garrow TA 1997 Diet-induced changes in hepatic betaine-homocysteine methyltransferase activity are mediated by changes in the steady-state level of its mRNA. J. Nutr. Biochem. 8 541–545

    Article  CAS  Google Scholar 

  • Quinkler M and Stewart PM 2003 Hypertension and the cortisol-cortisone shuttle. J. Clin. Endocrinol. Metab. 88 2384–2392

    Article  PubMed  CAS  Google Scholar 

  • Ratnam S, Wijekoon EP, Hall B, Garrow TA, Brosnan ME and Brosnan JT 2006 Effects of diabetes and insulin on betaine-homocysteine S-methyltransferase expression in rat liver. Am. J. Physiol. 290 E933–E939

    CAS  Google Scholar 

  • Schäfer C, Hoffmann L, Heldt K, Lornejad-Schäfer MR, Brauers G, Gehrmann T, Garrow TA, Häussinger D, Mayatepek E, Schwahn BC and Schliess F 2007 Osmotic regulation of betaine homocytine-S-methyltransferase expression in H4IIE rat hepatoma cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292 G1089–G1098

    Google Scholar 

  • Schliess F and Häussinger D 2002 The cellular hydration state: a critical determinant for cell death and survival. Biol. Chem. 383 577–583

    Article  PubMed  CAS  Google Scholar 

  • Sizeland PC, Chambers ST, Lever M, Bason LM and Robson RA 1995 Shortterm response of nonurea organic osmolytes in human kidney to a water load and water deprivation. Am. J. Physiol. Renal Fluid Electrolyte Physiol. 268 F227–F233

    Google Scholar 

  • Slow S and Garrow TA 2006 Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats. J. Nutr. 136 2279–2283

    PubMed  CAS  Google Scholar 

  • Sunden SLF, Renduchintala MS, Park EI, Miklasz SD and Garrow TA 1997 Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch. Biochem. Biophys. 345 171–174

    Article  PubMed  CAS  Google Scholar 

  • Sundström J, Sullivan L, D’Agostino RB, Jacques PF, Selhub J, Rosenberg IH, Wilson PWF, Levy D and Vasan RS 2003 Plasma homocysteine, hypertension incidence, and blood pressure tracking: the Framingham Heart Study. Hypertension 42 1100–1105

    Article  PubMed  Google Scholar 

  • Teng YW, Mehedint MG, Garrow TA and Zeisel SH 2011 Deletion of betaine-homocysteine s-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in Fatty liver and hepatocellular carcinomas. J. Biol. Chem. 286 36258–36267

    Google Scholar 

  • Wehner F, Olsen H, Tinel H, Kinne-Saffran E and Kinne RKH 2003 Cell volume regulation: osmolytes, osmolyte transport and signal transduction. Rev. Physiol. Biochem. Pharmacol. 148 1–80

    Article  PubMed  CAS  Google Scholar 

  • Zeisel SH and Blusztajn JK 1994 Choline and human nutrition. Annu. Rev. Nutr. 14 269–296

    Article  PubMed  CAS  Google Scholar 

  • Zeisel SH, Mar M-H, Howe JC and Holden JM 2003 Concentrations of choline-containing compounds and betaine in common foods. J. Nutr. 133 1302–1307

    PubMed  CAS  Google Scholar 

  • Zhang J, Blusztajn JK and Zeisel SH 1992 Measurement of the formation of betaine aldehyde and betaine in rat liver mitochondria by high pressure liquid chromatography-radioenzymatic assay. Biochim. Biophys. Acta 1117 333–339

    Google Scholar 

Download references

Acknowledgements

The authors wish to thank Dr José Burdman, for critically reviewing the manuscript, Dra. María A Pajares for the gift of the Anti-BHMT polyclonal antibodies (rabbit) and Bioq. José L D’Eramo for their technical assistance. This study was supported by a grant from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (PIP 5716), and by a grant from the Universidad Abierta Interamericana UAI. AVM, LEB, PCT-N and EAP have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana (UAI), Buenos Aires, Argentina

    Osvaldo Fridman, Analía V Morales, Paula C Turk-Noceto & Elio A Prieto

  2. Instituto de Oncología Ángel H Roffo, Buenos Aires, Argentina

    Osvaldo Fridman & Laura E Bortoni

  3. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina

    Osvaldo Fridman

Authors
  1. Osvaldo Fridman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Analía V Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura E Bortoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula C Turk-Noceto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elio A Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Osvaldo Fridman.

Additional information

[Fridman O, Morales AV, Bortoni LE, Turk-Noceto PC and Prieto EA 2012 Corticoadrenal activity regulates in rat betaine-homocysteine S-methyltransferase expression with opposites effects in liver and kidney. J. Biosci. 37 XXX–XXX] DOI

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fridman, O., Morales, A.V., Bortoni, L.E. et al. Corticoadrenal activity regulates in rat betaine-homocysteine S-methyltransferase expression with opposites effects in liver and kidney. J Biosci 37, 115–123 (2012). https://doi.org/10.1007/s12038-011-9171-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-011-9171-5

Keywords

Search

Navigation