Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos

Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos
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DOI:
10.1016/j.febslet.2006.04.020
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发表时间:
2006-05-15
期刊:
影响因子:
3.5
通讯作者:
Greene, Nicholas D. E.
Greene, Nicholas D. E.
中科院分区:
生物学3区
文献类型:
--
作者:
Dunlevy, Louisa P. E.;Burren, Katie A.;Greene, Nicholas D. E.

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单碳代谢抑制或蛋氨酸摄入不足可能增加神经管缺陷(NTD)的风险。在这里,外源性蛋氨酸意外地引起了培养小鼠胚胎中频繁的NTD。NTD与颅间充质细胞密度降低有关,这可能是由于先前增殖减少所致。在处理过的胚胎中,s -腺苷蛋氨酸与s -腺苷同型半胱氨酸的丰度比也降低了,表明甲基化反应可能受到抑制。这种效应具有潜在的致病性,因为当DNA甲基化被特异性抑制时,也观察到NTD。因此,颅间质密度的降低和关键甲基化反应的损害可能有助于蛋氨酸诱导的NTD的发展。(c) 2006年由Elsevier B.V.代表欧洲生化学会联合会出版。
Suppression of one-carbon metabolism or insufficient methionine intake are suggested to increase risk of neural tube defects (NTD). Here, exogenous methionine unexpectedly caused frequent NTD in cultured mouse embryos. NTD were associated with reduced cranial mesenchyme cell density, which may result from a preceding reduction in proliferation. The abundance ratio of S-adenosylmethionine to S-adenosylhomocysteine was also decreased in treated embryos, suggesting methylation reactions may be suppressed. Such an effect is potentially causative as NTD were also observed when DNA methylation was specifically inhibited. Thus, reduced cranial mesenchyme density and impairment of critical methylation reactions may contribute to development of methionine-induced NTD. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.