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Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

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Abstract

The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation.

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Abbreviations

BHMT:

Betaine:homocysteine methyltransferase

CDO:

Cysteine dioxygenase

CSAD:

Cysteine sulfinic acid decarboxylase

SHP:

Small heterodimer partner

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Authors and Affiliations

  1. Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA

    Halina Jurkowska, Julie Niewiadomski, Lawrence L. Hirschberger, Heather B. Roman, Kevin M. Mazor, Xiaojing Liu, Jason W. Locasale & Martha H. Stipanuk

  2. Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

    Halina Jurkowska

  3. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA

    Eunkyue Park

Authors
  1. Halina Jurkowska
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  2. Julie Niewiadomski
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  3. Lawrence L. Hirschberger
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  4. Heather B. Roman
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  5. Kevin M. Mazor
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  6. Xiaojing Liu
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  7. Jason W. Locasale
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  8. Eunkyue Park
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  9. Martha H. Stipanuk
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Corresponding author

Correspondence to Martha H. Stipanuk.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This project was supported by Grants DK056649, CA168997 and AI110613 from the National Institutes of Health and by the New York State Office for People with Developmental Disabilities. HJ was supported by a “Mobility Plus” fellowship from the Ministry of Science and Higher Education (MNISW), Republic of Poland. The content is solely the responsibility of the authors.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All experimental procedures involving Cdo1 +/− mice and their offspring were conducted with the approval of the Cornell University Institutional Animal Care and Use Committee (#2009-0138). All experimental procedures involving Csad-null mice were conducted with the approval of the Institutional Animal Care and Use Committee of the New York State Institute for Basic Research in Developmental Disabilities (#392).

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Jurkowska, H., Niewiadomski, J., Hirschberger, L.L. et al. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo. Amino Acids 48, 665–676 (2016). https://doi.org/10.1007/s00726-015-2108-9

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  • DOI: https://doi.org/10.1007/s00726-015-2108-9

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