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Abstract：
Human individual differences in brain cytochrome P450 (CYP) metabolism, including induction, inhibition, and genetic variation, may influence brain sensitivity to neurotoxins and thus participate in the onset of neurodegenerative diseases. The aim of this study was to explore the modulation of CYPs in neuronal cells. The experimental approach was focused on differentiating human neuroblastoma SH-SY5Y cells into a phenotype resembling mature dopamine neurons and investigating the effects of specific CYP isoform induction. The results demonstrated that the differentiation protocols using retinoic acid followed by phorbol esters or brain-derived neurotrophic factor successfully generated SH-SY5Y cells with morphological neuronal characteristics and increased neuronal markers (NeuN, synaptophysin, β-tubulin III, and MAO-B). qRT-PCR and Western blot analysis showed that expression of the CYP 1A1, 3A4, 2D6, and 2E1 isoforms was detectable in undifferentiated cells, with subsequent increases in CYP 2E1, 2D6, and 1A1 following differentiation. Further increases in the 1A1, 2D6, and 2E1 isoforms following β-naphthoflavone treatment and 1A1 and 2D6 isoforms following ethanol treatment were evident. These results demonstrate that CYP isoforms can be modulated in SH-SY5Y cells and suggest their potential as an experimental model to investigate the role of CYPs in neuronal processes involved in the development of neurodegenerative diseases.
摘要：
人类在脑细胞色素P450（CYP）代谢中的个体差异，包括归纳法,抑制,和遗传变异，可能会影响大脑对神经毒素的敏感性，从而参与神经退行性疾病的发作。本研究的目的是探索神经元细胞中CYPs的调节。实验方法的重点是将人神经母细胞瘤SH-SY5Y细胞分化为类似成熟多巴胺神经元的表型，并研究特定CYP同工型诱导的作用。结果表明，使用视黄酸和佛波醇酯或脑源性神经营养因子的分化方案成功地产生了具有形态神经元特征和增加的神经元标记的SH-SY5Y细胞（NeuN，突触素,β-微管蛋白III，和MAO-B）。qRT-PCR和Westernblot分析显示在未分化细胞中可检测到CYP1A1、3A4、2D6和2E1亚型的表达,分化后CYP2E1、2D6和1A1随后增加。β-萘黄酮处理后1A1，2D6和2E1同种型以及乙醇处理后1A1和2D6同种型的进一步增加是明显的。这些结果表明，CYP同工型可以在SH-SY5Y细胞中进行调节，并表明它们作为实验模型的潜力，可以研究CYP在涉及神经退行性疾病发展的神经元过程中的作用。
