Taurine-deficient diet up-regulated cystathionine beta-synthase monoallele in hemizygous cystathionine beta-synthase knockout mice.
Impaired cystathionine beta-synthase (CBS) causes hyperhomocystinuria and hyperhomocysteinemia, both risk factors for cardiovascular diseases. Reduced CBS activity could decrease cysteine and taurine biosyntheses (metabolites of homocysteine degradation) and lead to less taurocholic acid production with a resultant increased cholesterol content. We hypothesized that a deficiency in CBS genetic material and enzyme activity would reduce taurine synthesis, which would lead to an elevated cholesterol concentration. Both sexes of hemizygous C57BL/6J-Cbs(tm1Unc) [CBS (+/-)] and wild-type C57BL/6J mice [CBS (+/+)] were divided into 2 groups. One group of CBS (+/-) and CBS (+/+) mice was fed a cysteine- and taurine-deficient diet for 8 weeks, and the other group was fed a cysteine, taurine, and vitamin B6-deficient diet for 8 weeks. Significantly higher plasma total homocysteine concentrations occurred in the CBS (+/-) mice than their CBS (+/+) cohorts. Female mice of both genotypes had significantly higher plasma total homocysteine concentrations and significantly lower relative CBS mRNA levels than did male mice. During vitamin B(6) deficiency, plasma total homocysteine concentrations were significantly elevated. Three important findings were a differential sex response of CBS mRNA to feeding the vitamin B(6) diet; CBS (+/-) mice had a significantly lower plasma cholesterol concentration, contrary to what was anticipated; and during feeding, the taurine- and cysteine-deficient diet, CBS mRNA levels in CBS (+/-) mice were reduced only 13% rather than the expected 50%. We conclude that the remaining CBS monoallele is up-regulated in mice when fed a taurine-deficient diet to produce additional CBS mRNA.
Chao
Wei-Hsun
WH
Department of Early Childhood Educare, WuFeng Institute of Technology, Ming-Hsiung, Chia-Yi, Taiwan, ROC. whchao@mail.wfc.edu.tw
Reynolds
Robert D
RD
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000172:deficiency; D004032:Diet; D005260:Female; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D013654:Taurine / Q000096:biosynthesis / Q000172:deficiency*; D013656:Taurocholic Acid / Q000096:biosynthesis; D015854:Up-Regulation; D026681:Vitamin B 6 Deficiency / Q000097:blood*
D012333:RNA, Messenger; D006710:Homocysteine; D013654:Taurine; D013656:Taurocholic Acid; D002784:Cholesterol; D003541:Cystathionine beta-Synthase; D003545:Cysteine