Brain-derived neurotrophic factor induces thioredoxin-1 expression through TrkB/Akt/CREB pathway in SH-SY5Y cells

Brain-derived neurotrophic factor induces thioredoxin-1 expression through TrkB/Akt/CREB pathway in SH-SY5Y cells
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脑源性神经营养因子通过 TrkB/Akt/CREB ​​通路诱导 SH-SY5Y 细胞中硫氧还蛋白-1 的表达。

DOI:
10.1016/j.biochi.2019.02.011
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发表时间:
2019-05-01
期刊:
影响因子:
3.9
通讯作者:
Bai, Jie
Bai, Jie
中科院分区:
生物学3区
文献类型:
--
作者:
Bai, Liping;Zhang, Se;Bai, Jie

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脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)是对神经元的存活和增殖起重要作用的神经营养因子之一。硫氧还蛋白-1(Thioredoxin-1,Trx-1)是一种氧化还原调节蛋白,在调节转录因子和抑制细胞凋亡中发挥多种作用。有报道称Trx-1是神经生长因子介导的信号转导和轴突生长所必需的,并参与BDNF诱导的突触蛋白表达。然而,BDNF诱导Trx-1表达的分子机制尚未完全证实。本研究探讨了BDNF处理SH-SY 5 Y细胞后Trx-1的表达。我们首先证明,在SH-SY 5 Y细胞中,BDNF增加细胞活力和Trx-1的表达,这被酪氨酸激酶B(Trk B)抑制剂K252 a和磷脂酰肌醇3-激酶(PI 3-K)抑制剂LY 294002抑制。BDNF还通过TrkB/PI 3-K/Akt途径增加cAMP反应元件结合蛋白(CREB)的活性。而CREB siRNA则抑制BDNF诱导的Trx-1表达。因此,我们的数据表明,BDNF通过TrkB/Akt/CREB途径诱导Trx-1的表达。(C)2019 Elsevier B. V.和法国生物化学与生物分子学会(SFBBM)。All rights reserved.
Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that are vital to the survival and proliferation of neuron. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays various roles in regulating transcript factors and inhibiting apoptosis. It has been reported that Trx-1 is required for nerve growth factor-mediated signal transduction and neurite outgrowth, and is involved in synaptic protein expression induced by BDNF. However, the molecular mechanism on BDNF inducing Trx-1 expression has not been fully verified. The present study investigated the expression of Trx-1 after treatment with BDNF in SH-SY5Y cells. We first demonstrated that cell viability and the expression of Trx-1 were increased by BDNF in SH-SY5Y cells, which were inhibited by the tyrosine kinase B (TrkB) inhibitor, K252a, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. Moreover, BDNF increased the activity of cAMP response element-binding protein (CREB) through TrkB/PI3-K/Akt pathway. Whereas the expression of Trx-1 induced by BDNF was suppressed by CREB siRNA. Thus, our data suggest that BDNF induces the expression of Trx-1 through the TrkB/Akt/CREB pathway. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.