Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research
Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research
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DOI：
10.1016/j.neuro.2008.11.001
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发表时间：
2009-01-01
期刊：
影响因子：
3.4
通讯作者：
Chang, Raymond Chuen-Chung
中科院分区：
文献类型：
--
作者：
Cheung, Yuen-Ting;Lau, Way Kwok-Wai;Chang, Raymond Chuen-Chung
人神经母细胞瘤SH-SY 5 Y是一种多巴胺能神经元细胞系，已被用作神经毒性实验的体外模型。虽然神经母细胞瘤通常是由全反式维甲酸（RA）分化，RA分化和未分化的SH-SY 5 Y细胞已被用于神经科学研究。然而，由RA引发的神经元特性的变化以及随后对神经毒素的反应性尚未得到全面研究。因此，我们的目的是重新评估RA在该细胞系上的分化特性。我们推测，RA介导的SH-SY 5 Y细胞分化过程中信号通路和神经元特性的调节可以影响其对神经毒素的易感性。RA的分化特性被证实，表现出广泛的突起，神经元核，神经元特异性烯醇化酶，突触素和突触相关蛋白-97的表达增加，和分化抑制因子-1的表达减少。虽然未分化的SH-SY 5 Y细胞对6-OHDA和MPP+敏感，但RA分化赋予SH-SY 5 Y细胞更高的耐受性，这可能是通过上调存活信号传导，包括Akt途径，因为Akt的抑制消除了RA诱导的针对6-OHDA的神经保护。因此，在RA分化的细胞中不能揭示真实的毒性。因此，未分化的SH-SY 5 Y更适合于在实验性帕金森病研究中研究神经毒性或神经保护作用。(C)2008年爱思唯尔公司All rights reserved.
Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all-trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP+, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore,undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research. (C) 2008 Elsevier Inc. All rights reserved.