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Publication year
2005Source
Developmental Brain Research, 158, 1-2, (2005), pp. 59-65ISSN
Publication type
Article / Letter to editor

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Organization
Paediatrics - OUD tm 2017
Journal title
Developmental Brain Research
Volume
vol. 158
Issue
iss. 1-2
Page start
p. 59
Page end
p. 65
Subject
IGMD 3: Genomic disorders and inherited multi-system disorders; NCEBP 14: Cardiovascular diseases; NCMLS 4: Energy and redox metabolism; UMCN 2.2: Vascular medicine and diabetesAbstract
Periconceptional folic acid supplementation can reduce the occurrence of neural tube defects. A low folate status will result in reduced remethylation of homocysteine (Hcy) to methionine and, subsequently, in a rise of Hcy levels. Indeed, elevated Hcy concentrations have been reported in mothers of children with neural tube defects. In our previous study, we showed that treatment of chick embryos with Hcy resulted in a delay of neural tube closure in an in vitro model. In the present study, we examined whether this effect of Hcy is due to inhibition of transmethylation via elevation of S-adenosylhomocysteine (AdoHcy). Transmethylation involves methylation of DNA, RNA and proteins by donation of a methyl group from S-adenosylmethionine (AdoMet). After application of inhibitors of S-adenosylhomocysteine hydrolase and of methionine adenosyltransferase, a delay of anterior neuropore closure, comparable to that observed after Hcy treatment, was observed. The changes in AdoMet and AdoHcy concentrations confirmed the inhibition of S-adenosylhomocysteine hydrolase or methionine adenosyltransferase, respectively, and the AdoMet/AdoHcy ratio was decreased in all cases, indicating reduced transmethylation. Moreover, the inhibition of methionine adenosyltransferase was prevented by pretreatment with methionine. This study, therefore, indicates that the Hcy-induced delay of the neural tube closure is caused by the inhibition of transmethylation via elevation of AdoHcy levels and a reduction of the AdoMet/AdoHcy ratio.
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- Academic publications [227425]
- Electronic publications [107155]
- Faculty of Medical Sciences [86157]
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