Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Molecular Neuropharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Cell Mol Biol Lett. 2021 Feb 15;26(1):5. doi: 10.1186/s11658-020-00243-8.
The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer's and Parkinson's disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation.
Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed.
The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells.
The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.
突触小泡糖蛋白 2(SV2)家族对于涉及神经递质传递和囊泡再循环的突触机制至关重要。SV2A、SV2B 和 SV2C 同工型与癫痫、阿尔茨海默病和帕金森病等神经疾病有关。研究这些蛋白质调节的合适细胞系统是必不可少的。在这里,我们展示了两种人神经母细胞瘤细胞系 SiMa 和 IMR-32 在分化后 SV2A、SV2B 和 SV2C 的基因表达数据。
用人神经母细胞瘤细胞系 SiMa 和 IMR-32 用生长补充剂(B-27 和 N-2)、全反式视黄酸(ATRA)或血管活性肠肽(VIP)处理七天,分析 SV2 和神经元靶标基因的表达水平。
两种细胞系对处理的反应不同,并且只有三个 SV2 同工型之一一次受到影响。生长补充处理后,SV2B 和胆碱 O-乙酰转移酶(CHAT)的表达协同变化,SiMa 细胞中减少,而 IMR-32 中增加。ATRA 处理在两种细胞系中均未检测到 SV2 表达的变化,而 VIP 增加了 IMR-32 细胞中的 SV2C 和多巴胺转运体(DAT)。
SV2B 和 CHAT 之间以及 SV2C 和 DAT 之间的协同表达模式反映了在疾病模型和基因敲除动物中发现的这些靶标之间的连接性,尽管这里没有进行遗传改变。这些细胞系和分化处理可能可用于研究 SV2 的调节和功能。