The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway
The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway
复制标题
牛磺酸通过Wnt/PCP-Jnk依赖性途径对神经管缺陷的预防作用
DOI：
10.1007/s00726-017-2462-x
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发表时间：
2017-09-01
期刊：
影响因子：
3.5
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Zhang, Qinghua;Liu, Yang;Zhang, Li
本研究的目的是阐明牛磺酸在神经细胞凋亡中的保护作用以及Wnt/PCP-JNK通路在牛磺酸预防神经管缺陷（NTDs）中的作用。将HT-22细胞分为对照组、谷氨酸诱导凋亡组、谷氨酸（4.0 mmol/L）+低剂量牛磺酸（L; 0.5 mmol/L）组和高剂量牛磺酸（H; 2.0 mmol/L）组。MTT法检测细胞增殖和存活情况。免疫荧光和Western blot分析用于确定caspase 9表达。用维甲酸（RA）诱导昆明种小鼠胚胎NTD，建立NTD模型。将妊娠小鼠分为对照组、RA（30 mg/kg体重）组和RA（30 mg/kg体重）+牛磺酸（自由饮用2 g/L溶液）组。免疫组化和Western blot检测Dvl、RhoA和磷酸化（p）-JNK/JNK在胚胎神经管中的表达。在HT-22细胞中，与L和H牛磺酸组相比，谷氨酸诱导的凋亡组的凋亡率显著更高，caspase 9的活化也显著增加。在NTD模型中，RA组中Dvl、RhoA和p-Jnk的表达水平显著高于对照组，而RA +牛磺酸组中Dvl、RhoA和p-Jnk的表达水平显著降低。这项研究表明，牛磺酸对神经元保护和NTD预防具有积极作用。此外，Wnt/PCP-Jnk依赖性途径在牛磺酸介导的NTD预防中起重要作用。
The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.