Rana Birju, Veal Gareth J, Pearson Andrew D J, Redfern Christopher P F
Department of Endocrinology, Medical Molecular Biology Group, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
J Cell Biochem. 2002;86(1):67-78. doi: 10.1002/jcb.10192.
Retinoic acid (RA) modulates differentiation and apoptosis of neural cells via RA receptors (RARs) and retinoid X receptors (RXRs). Neuroblastoma cells are potentially useful models for elucidating the molecular mechanisms of RA in neural cells, and responses to different isomers of RA have been interpreted in terms of differential homo- and heterodimerization of RXRs. The aim of this study was to identify the RXR types expressed in neuroblast and substrate-adherent neuroblastoma cells, and to study the participation of these RXRs in RAR heterodimers. RXRbeta was the predominant RXR type in N-type SH SY 5Y cells and S-type SH EP cells. Gel shift and supershift assays demonstrated that RARbeta and RARgamma predominantly heterodimerize with RXRbeta. In SH SY 5Y cells, RARgamma/RXRbeta was the predominant heterodimer binding to the DR5 RARE in the absence of 9-cis RA (9C), whereas the balance shifted in favor of RARbeta/RXRbeta in the presence of ligand. There was a marked difference between the N- and S-type neuroblastoma cells in retinoid receptor-DNA interactions, and this may underlie the differential effects of retinoids in these neuroblastoma cell types. There was no evidence to indicate that 9C functions via RXR homodimers in either SH SY 5Y or SH EP neuroblastoma cells. The results of this study suggest that interactions between retinoid receptors and other nuclear proteins may be critical determinants of retinoid responses in neural cells.
视黄酸（RA）通过视黄酸受体（RARs）和类视黄醇X受体（RXRs）调节神经细胞的分化和凋亡。神经母细胞瘤细胞是阐明RA在神经细胞中分子机制的潜在有用模型，并且对RA不同异构体的反应已根据RXRs的不同同源和异源二聚化来解释。本研究的目的是鉴定在神经母细胞和贴壁神经母细胞瘤细胞中表达的RXR类型，并研究这些RXRs在RAR异源二聚体中的参与情况。RXRβ是N型SH SY 5Y细胞和S型SH EP细胞中主要的RXR类型。凝胶迁移和超迁移分析表明，RARβ和RARγ主要与RXRβ异源二聚化。在SH SY 5Y细胞中，在没有9-顺式视黄酸（9C）的情况下，RARγ/RXRβ是与DR5 RARE结合的主要异源二聚体，而在存在配体的情况下，平衡向有利于RARβ/RXRβ的方向转变。N型和S型神经母细胞瘤细胞在类视黄醇受体与DNA的相互作用上存在显著差异，这可能是类视黄醇在这些神经母细胞瘤细胞类型中产生不同作用的基础。没有证据表明9C在SH SY 5Y或SH EP神经母细胞瘤细胞中通过RXR同源二聚体发挥作用。本研究结果表明，类视黄醇受体与其他核蛋白之间的相互作用可能是神经细胞中类视黄醇反应的关键决定因素。
