Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo.
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.
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.|Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.
Halina
H
Jurkowska
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Julie
J
Niewiadomski
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Lawrence L
LL
Hirschberger
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Heather B
HB
Roman
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Kevin M
KM
Mazor
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Xiaojing
X
Liu
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
Jason W
JW
Locasale
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Eunkyue
E
Park
Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA. mhs6@cornell.edu.
Martha H
MH
Stipanuk
D000818:Animals; D001622:Betaine / Q000378:metabolism*; D050558:Cysteine Dioxygenase / Q000235:genetics; D019587:Dietary Supplements / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000378:metabolism; D050904:Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013654:Taurine / Q000172:deficiency*
D013654:Taurine; D001622:Betaine; D050558:Cysteine Dioxygenase; D050904:Homocysteine S-Methyltransferase
Betaine; Betaine:homocysteine methyltransferase; Cysteine dioxygenase; Cysteine sulfinic acid decarboxylase; Hepatocytes; Liver; Taurine