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Identification of Taurine-Responsive Genes in Murine Liver Using the Cdo1-Null Mouse Model

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Taurine 10

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 975))

Abstract

The cysteine dioxygenase (Cdo1)-null mouse is unable to synthesize hypotaurine and taurine by the cysteine/cysteine sulfinate pathway and has very low taurine levels in all tissues. The lack of taurine is associated with a lack of taurine conjugation of bile acids, a dramatic increase in the total and unconjugated hepatic bile acid pools, and an increase in betaine and other molecules that serve as organic osmolytes. We used the Cdo1-mouse model to determine the effects of taurine deficiency on expression of proteins involved in sulfur amino acid and bile acid metabolism. We identified cysteine sulfinic acid decarboxylase (Csad), betaine:homocysteine methytransferase (Bhmt), cholesterol 7α-hydroxylase (Cyp7a1), and cytochrome P450 3A11 (Cyp3a11) as genes whose hepatic expression is strongly regulated in response to taurine depletion in the Cdo1-null mouse. Dietary taurine supplementation of Cdo1-null mice restored hepatic levels of these four proteins and their respective mRNAs to wild-type levels, whereas dietary taurine supplementation had no effect on abundance of these proteins or mRNAs in wild-type mice.

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Abbreviations

ABCB11:

ATP-binding cassette, subfamily B, member 11

BHMT:

Betaine:homocysteine methytransferase

CDO:

Cysteine dioxygenase

CSAD:

Cysteine sulfinic acid decarboxylase

CYP27A1:

Sterol 27-hydroxylase (cytochrome P450, family 27, subfamily A, member 1)

CYP3A11:

Cytochrome P450, family 3, subfamily A, member 11

CYP7A1:

Cholesterol 7α-hydroxylase (cytochrome P450, family 7, subfamily A, member 1)

FXR:

Farnesoid X receptor

LRH1:

Liver receptor homolog 1

OSTα-OSTβ:

Organic solute and steroid transporter

SHP:

Small heterodimer partner (also known as NR0B2)

SLC6A6:

Sodium- and chloride-dependent taurine transporter (also known as TAUT)

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Acknowledgments

This project was supported by National Institutes of Health Grant R01 DK056649. 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. We thank Dr. Jason W. Locasale and Dr. Xiaojing Liu for running the metabolomics profile.

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Authors and Affiliations

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

    Martha H. Stipanuk, Halina Jurkowska, Julie Niewiadomski, Kevin M. Mazor, Heather B. Roman & Lawrence L. Hirschberger

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

    Halina Jurkowska

Authors
  1. Martha H. Stipanuk
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  2. Halina Jurkowska
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  3. Julie Niewiadomski
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  4. Kevin M. Mazor
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  5. Heather B. Roman
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  6. Lawrence L. Hirschberger
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Corresponding author

Correspondence to Martha H. Stipanuk .

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Editors and Affiliations

  1. Department of Life Sciences, University of Seoul, Seoul, South Korea

    Dong-Hee Lee  & Ha Won Kim  & 

  2. College of Medicine, University of South Alabama, Mobile, Alabama, USA

    Stephen W. Schaffer

  3. Department of Developmental Neurobiology, NY State Institute for Basic Research in Developmental Disabilities, New York, USA

    Eunkyue Park

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Stipanuk, M.H., Jurkowska, H., Niewiadomski, J., Mazor, K.M., Roman, H.B., Hirschberger, L.L. (2017). Identification of Taurine-Responsive Genes in Murine Liver Using the Cdo1-Null Mouse Model. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_38

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