Taurine-deficient diet up-regulated cystathionine β -synthase monoallele in hemizygous cystathionine β -synthase knockout mice

Abstract Impaired cystathionine β -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 prod...

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Bibliographic Details
Published in:Nutrition research (New York, N.Y.) N.Y.), 2009-11, Vol.29 (11), p.794-801
Main Authors: Chao, Wei-Hsun, Reynolds, Robert D
Format: Article
Language:English
Subjects:
alleles
animal models
Animals
Biological and medical sciences
biosynthesis
Cardiovascular disease
cardiovascular diseases
CBS knockout
CBS mRNA
Cholesterol
Cholesterol - blood
cystathionine beta-synthase
Cystathionine beta-Synthase - deficiency
Cystathionine beta-Synthase - genetics
Cystathionine beta-Synthase - metabolism
cysteine
Cysteine - deficiency
Diet
Feeding. Feeding behavior
Female
females
Fundamental and applied biological sciences. Psychology
Gastroenterology and Hepatology
gene expression regulation
Heterozygote
Homocysteine
Homocysteine - blood
hyperhomocysteinemia
hyperhomocystinuria
Liver - metabolism
Male
males
Mice
Mice, Inbred C57BL
Mice, Knockout
monoallele
nutrient deficiencies
pyridoxine
risk factors
RNA, Messenger - metabolism
Sex Factors
Taurine
Taurine - biosynthesis
Taurine - deficiency
taurocholic acid
Taurocholic Acid - biosynthesis
Up-Regulation
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vitamin B 6 Deficiency - blood
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Summary:Abstract Impaired cystathionine β -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-Cbstm1Unc [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 B6 deficiency, plasma total homocysteine concentrations were significantly elevated. Three important findings were a differential sex response of CBS mRNA to feeding the vitamin B6 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.
ISSN:0271-5317
1879-0739
DOI:10.1016/j.nutres.2009.10.005