title: Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats.
abstract: OBJECTIVE
  The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation.
  
  
  METHODS
  Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection.
  
  
  RESULTS
  Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p=0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio=15.75, p=0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio=17.07, p=0.0006, and odds ratio=7.31, p=0.006, respectively).
  
  
  CONCLUSIONS
  Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.
authors.affiliation: Cellular and Molecular Pathology in Nutrition, EMI, INSERM 0014, URM IFREMER 20, CHU Nancy-Brabois, Vandoeuvre-lès-Nancy, Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brunaud
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alberto
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ayav
authors.forename: Philippe
authors.initials: P
authors.lastname: Gérard
authors.forename: Farès
authors.initials: F
authors.lastname: Namour
authors.forename: Laurent
authors.initials: L
authors.lastname: Antunes
authors.forename: Marc
authors.initials: M
authors.lastname: Braun
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Laurent
authors.initials: L
authors.lastname: Bresler
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism*; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D005494:Folic Acid Deficiency / Q000503:physiopathology; D005743:Gastrectomy; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014806:Vitamin B 12 Deficiency / Q000503:physiopathology*
chemical_list: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase