Brunaud Laurent, Alberto Jean-Marc, Ayav Ahmet, Gérard Philippe, Namour Farès, Antunes Laurent, Braun Marc, Bronowicki Jean-Pierre, Bresler Laurent, Guéant Jean-Louis
Cellular and Molecular Pathology in Nutrition, EMI, INSERM 0014, URM IFREMER 20, CHU Nancy-Brabois, Vandoeuvre-lès-Nancy, Nancy, France.
Digestion. 2003;68(2-3):133-40. doi: 10.1159/000075307. Epub 2003 Nov 28.
BACKGROUND/AIMS: 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.
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.
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).
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.
背景/目的：叶酸和维生素B12缺乏对甲硫氨酸合成酶（MTR）活性、转录及DNA甲基化的各自影响尚未明确。本研究旨在评估叶酸和维生素B12缺乏对MTR转录、活性及DNA甲基化的各自影响。
61只大鼠分别给予正常饮食或缺乏胆碱、蛋氨酸、叶酸和维生素B12的饮食。其中47只大鼠接受了全胃切除术或回肠切除术。
仅在接受胃切除术的大鼠中观察到维生素B12水平低。在缺乏饮食的大鼠中观察到叶酸水平低。仅当维生素B12水平<200 pmol/l时，总MTR活性（全酶+脱辅基酶）降低（p = 0.0002），而总MTR活性与全酶MTR活性的比值以及转录本MTR与甘油醛-3-磷酸脱氢酶（GAPDH）的比值（逆转录-聚合酶链反应）未改变。维生素B12是低MTR的唯一决定因素（下四分位数，优势比=15.75，p = 0.0017）。低MTR和低维生素B12是DNA低甲基化（下四分位数）的两个决定因素（优势比分别为17.07，p = 0.0006和7.31，p = 0.006）。
维生素B12通过不同于对MTR蛋白水解的保护作用的非转录机制影响MTR表达。它也是DNA低甲基化的重要决定因素。
