Unit of Functional and Adaptative Biology, University of Paris Diderot, Sorbonne Paris Cité, EAC-CNRS 4413, 75013 Paris, France.
J Mol Neurosci. 2013 May;50(1):1-6. doi: 10.1007/s12031-012-9835-0. Epub 2012 Jun 15.
Hyperhomocysteinemia is associated with brain disease. However, biological actions linking hyperhomocysteinemia to neuronal abnormalities are not well understood. We recently found a relationship between Dyrk1A protein expression, a serine/threonine kinase that might be responsible for cognitive functions in Down's syndrome, and hepatic S-adenosylhomocysteine hydrolase (SAHH) activity, which plays a key role in S-adenosylmethionine-dependent methylation reactions. Considering the role of methylation and Dyrk1A in cognitive functions, the aim of this study was to investigate the relationship between Dyrk1A and SAHH activity in brain of hyperhomocysteinemic mice. We found an increase in Dyrk1A protein expression and activity in brain of hyperhomocysteinemic mice, concomitant with an increased SAHH activity. The effect of overexpression of protein Dyrk1A on SAHH activity was confirmed in brain of Dyrk1A transgenic mice, and additionally we found a positive correlation between Dyrk1A and SAHH activity. These observations suggest a potential effect of Dyrk1A on brain phenotypes linked to hyperhomocysteinemia.
高同型半胱氨酸血症与脑部疾病有关。然而，高同型半胱氨酸血症与神经元异常之间的生物学作用尚不清楚。我们最近发现 Dyrk1A 蛋白表达与肝 S-腺苷同型半胱氨酸水解酶（SAHH）活性之间存在关系，Dyrk1A 是一种丝氨酸/苏氨酸激酶，可能与唐氏综合征的认知功能有关，而 SAHH 活性在 S-腺苷甲硫氨酸依赖性甲基化反应中起着关键作用。鉴于甲基化和 Dyrk1A 在认知功能中的作用，本研究旨在探讨高同型半胱氨酸血症小鼠大脑中 Dyrk1A 和 SAHH 活性之间的关系。我们发现高同型半胱氨酸血症小鼠大脑中的 Dyrk1A 蛋白表达和活性增加，同时 SAHH 活性也增加。在 Dyrk1A 转基因小鼠的大脑中，证实了蛋白 Dyrk1A 对 SAHH 活性的过表达作用，并且还发现 Dyrk1A 与 SAHH 活性之间存在正相关。这些观察结果表明 Dyrk1A 可能对与高同型半胱氨酸血症相关的脑部表型有潜在影响。
