Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 Beta.
Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 Beta.
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DOI：
10.1007/s12640-009-9036-y
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发表时间：
2009-05
影响因子：
3.7
通讯作者：
Luo, Jia
中科院分区：
文献类型：
--
作者：
Chen, Gang;Bower, Kimberly A.;Xu, Mei;Ding, Min;Shi, Xianglin;Ke, Zun-Ji;Luo, Jia
乙醇是中枢神经系统发育的一种强致畸剂，胎儿酒精综合征是智力低下最常见的非遗传性原因。乙醇破坏神经元的分化和成熟。重要的是，以确定代理，提供神经保护乙醇神经毒性。使用体外神经元模型，小鼠Neuro 2a（N2 a）神经母细胞瘤细胞，我们证明了乙醇抑制神经突起生长和神经丝（NF）蛋白的表达。糖原合成酶激酶3β（Glycogen synthase kinase 3 β，GSK 3 β）是一种多功能丝氨酸/苏氨酸激酶，可负调控N2 a细胞的神经突生长;通过维甲酸（RA）和锂抑制GSK 3 β活性可诱导神经突生长，而组成型活性S9 A GSK 3 β突变体的过表达可阻止神经突生长。乙醇通过GSK 3 β在丝氨酸9的去磷酸化激活GSK 3 β来抑制神经突生长。花青素-3-葡萄糖苷（Cyanidin-3-glucoside，C3 G）是花青素家族的一员，在许多可食用的浆果和其他有色水果中富含，通过促进p-GSK 3 β（Ser 9）来增强神经突的生长。更重要的是，C3 G逆转了乙醇介导的GSK 3 β激活和对神经突起生长以及NF蛋白表达的抑制。C3 G还阻断乙醇诱导的细胞内活性氧（ROS）的积累。然而，C3 G的抗氧化作用似乎很少参与其保护作用。我们的研究为预防或改善乙醇对发育中的CNS的损伤提供了一个潜在的途径。
Ethanol is a potent teratogen for the developing central nervous system (CNS), and fetal alcohol syndrome (FAS) is the most common nonhereditary cause of mental retardation. Ethanol disrupts neuronal differentiation and maturation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Using an in vitro neuronal model, mouse Neuro2a (N2a) neuroblastoma cells, we demonstrated that ethanol inhibited neurite outgrowth and the expression of neurofilament (NF) proteins. Glycogen synthase kinase 3β (GSK3β), a multi-functional serine/threonine kinase negatively regulated neurite outgrowth of N2a cells; inhibiting GSK3β activity by retinoic acid (RA) and lithium induced neurite outgrowth, while over-expression of a constitutively active S9A GSK3β mutant prevented neurite outgrowth. Ethanol inhibited neurite outgrowth by activating GSK3β through the dephosphorylation of GSK3β at serine 9. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family rich in many edible berries and other pigmented fruits, enhanced neurite outgrowth by promoting p-GSK3β(Ser9). More importantly, C3G reversed ethanol-mediated activation of GSK3β and inhibition of neurite outgrowth as well as the expression of NF proteins. C3G also blocked ethanol-induced intracellular accumulation of reactive oxygen species (ROS). However, the antioxidant effect of C3G appeared minimally involved in its protection. Our study provides a potential avenue for preventing or ameliorating ethanol-induced damage to the developing CNS.
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影响因子：
4.7
作者：
Luo, J;Lindström, CLB;Miller, MW
通讯作者：
Miller, MW
影响因子：
8
作者：
de la Monte, SM;Wands, JR
通讯作者：
Wands, JR
影响因子：
4.7
作者：
De Girolamo, LA;Billett, EE;Hargreaves, AJ
通讯作者：
Hargreaves, AJ
影响因子：
4.8
作者：
Chen, G;Bower, KA;Luo, J
通讯作者：
Luo, J
DOI：
10.1073/pnas.0610068104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Dasgupta, Biplab;Milbrandt, Jeffrey
通讯作者：
Milbrandt, Jeffrey