A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells
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DOI：
10.1186/1471-2164-10-543
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发表时间：
2009-11-19
期刊：
影响因子：
4.4
通讯作者：
Gustincich, Stefano
中科院分区：
文献类型：
--
作者：
Calligaris, Raffaella;Bellarosa, Cristina;Gustincich, Stefano
背景资料：未结合胆红素（UCB）在大脑特定区域的沉积导致不可逆的神经元损伤，或胆红素脑病（BE）。尽管UCB会损害其他组织的大量细胞功能，但神经毒性的基本机制尚未完全阐明。虽然细胞可以积累UCB被动扩散，细胞保护可能涉及多种机制，包括挤压的色素，以及前生存的稳态responses that is still unknow.Results：转录组的变化诱导UCB曝光在SH-SY 5 Y神经母细胞瘤细胞系进行了检查高密度寡核苷酸芯片。24小时后诱导了230个基因。基因本体（GO）分析表明，至少有50个基因直接参与内质网（ER）应激反应。通过定量RT-PCR显示所选ER应激基因的验证。XBP 1剪接和DDIT 3/CHOP亚细胞定位的分析presented.Conclusion：这些结果首次表明，UCB暴露诱导ER应激反应作为主要的细胞内稳态在体外存活的神经母细胞瘤细胞。
Background: The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown.Results: Transcriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER) stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis of XBP1 splicing and DDIT3/CHOP subcellular localization is presented.Conclusion: These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro.