Heidenreich David J, Reedy Mark V, Brauer Philip R
Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, USA.
Dev Dyn. 2008 Aug;237(8):2117-28. doi: 10.1002/dvdy.21644.
Elevated homocysteine (Hcys) increases the risk of neurocristopathies. Previous studies show Hcys inhibits neural crest (NC) cell migration in vivo. However, the mechanisms responsible for this effect are unknown. Here, we evaluated the effect of Hcys on NC cell attachment in vitro and determined if any of the effects were due to altered Ca2+ signaling. We found Hcys enhanced NC cell attachment in a dose and substrate-dependent manner. Ionomycin mimicked the effect of Hcys while BAPTA-AM and 2-APB blocked the effect of Hcys on NC attachment. In contrast, inhibitors of plasma membrane Ca2+ channels had no effect on NC attachment. Hcys also increased the emission of the intracellular Ca2+-sensitive probe, Fluo-4. These results show Hcys alters NC attachment by triggering an increase in intracellular Ca2+ possibly by generating inositol triphosphate. Hence, the teratogenic effect ascribed to Hcys may be due to perturbation of intracellular Ca2+ signaling.
同型半胱氨酸（Hcys）水平升高会增加神经嵴病的风险。先前的研究表明，Hcys在体内会抑制神经嵴（NC）细胞的迁移。然而，导致这种效应的机制尚不清楚。在此，我们评估了Hcys对体外NC细胞黏附的影响，并确定是否有任何效应是由于Ca2+信号改变所致。我们发现Hcys以剂量和底物依赖的方式增强了NC细胞的黏附。离子霉素模拟了Hcys的作用，而BAPTA-AM和2-APB则阻断了Hcys对NC黏附的影响。相比之下，质膜Ca2+通道抑制剂对NC黏附没有影响。Hcys还增加了细胞内Ca2+敏感探针Fluo-4的荧光发射。这些结果表明，Hcys可能通过生成肌醇三磷酸触发细胞内Ca2+增加，从而改变NC黏附。因此，归因于Hcys的致畸效应可能是由于细胞内Ca2+信号的扰动。
