Genetics and Genomic Medicine, GOS Institute of Child Health, University College London, London, UK; Biochemistry Division, Faculty of Science, Kuwait University, Kuwait.
Development Biology and Cancer, GOS Institute of Child Health, University College London, London, UK.
Neurochem Int. 2021 May;145:105009. doi: 10.1016/j.neuint.2021.105009. Epub 2021 Mar 5.
Parkinson's disease is a multifactorial neurodegenerative disease. The cellular pathology includes dopamine depletion, decrease in mitochondrial complex I enzyme activity, lysosomal glucocerebrosidase enzyme activity and glutathione levels. The SH-SY5Y human neuroblastoma cell line is one of the most widely used cell line models for Parkinson's disease. However, the consensus on its suitability as a model in its proliferative or differentiated state is lacking. In this study, we characterized and compared the biochemical processes most often studied in PD. This in proliferative and differentiated phenotypes of SH-SY5Y cells and several differences were found. Most notably, extracellular dopamine metabolism was significantly higher in differentiated SH-SY5Y. Furthermore, there was a greater variability in glutathione levels in proliferative phenotype (+/- 49%) compared to differentiated (+/- 16%). Finally, enzyme activity assay revealed significant increase in the lysosomal enzyme glucocerebrosidase activity in differentiated phenotype. In contrast, our study has found similarities between the two phenotypes in mitochondrial electron transport chain activity and tyrosine hydroxylase protein expression. The results of this study demonstrate that despite coming from the same cell line, these cells possess some key differences in their biochemistry. This highlights the importance of careful characterization of relevant disease pathways to assess the suitability of cell lines, such as SH-SY5Y cells, for modelling PD or other diseases, i.e. when using the same cell line but different differentiation states.
帕金森病是一种多因素神经退行性疾病。细胞病理学包括多巴胺耗竭、线粒体复合物 I 酶活性降低、溶酶体葡萄糖脑苷脂酶活性和谷胱甘肽水平降低。SH-SY5Y 人神经母细胞瘤细胞系是帕金森病最广泛使用的细胞系模型之一。然而，关于其在增殖或分化状态下作为模型的适用性缺乏共识。在这项研究中，我们对最常用于 PD 研究的生化过程进行了表征和比较。在增殖和分化的 SH-SY5Y 细胞中发现了几种差异。最值得注意的是，分化的 SH-SY5Y 中细胞外多巴胺代谢明显更高。此外，在增殖表型中（+/-49%），谷胱甘肽水平的变异性比分化表型（+/-16%）更大。最后，酶活性测定显示，分化表型中溶酶体酶葡萄糖脑苷脂酶活性显著增加。相比之下，我们的研究发现两种表型在线粒体电子传递链活性和酪氨酸羟化酶蛋白表达方面存在相似之处。这项研究的结果表明，尽管源自同一细胞系，但这些细胞在其生化特性上存在一些关键差异。这强调了仔细表征相关疾病途径以评估细胞系（如 SH-SY5Y 细胞）在模拟 PD 或其他疾病中的适用性的重要性，例如在使用相同细胞系但不同分化状态时。
