Sección Genética Evolutiva, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
J Mol Neurosci. 2011 Oct;45(2):76-86. doi: 10.1007/s12031-010-9389-y. Epub 2010 May 27.
Thyroid hormone has long been known to regulate neural development. Hypothyroidism during pregnancy and early postnatal period has severe neurological consequences including even mental retardation. The purpose of this study was to characterize gene expression pattern during thyroid hormone-induced differentiation of neuro-2a β cells in order to select "direct response genes" for further analysis. In this neuroblastoma cell line, thyroid hormone blocks proliferation and induces differentiation. Changes in gene expression level were examined after a T3 treatment of 3 and 24 h using cDNA arrays. Sixteen genes were significantly up-regulated and 79 down-regulated by T3 treatment. Five up-regulated genes not previously described as regulated by thyroid hormone and selected for their putative significance to understand T3 action on cell differentiation, were verified by RT-PCR analysis. The transcription factors Phox2a and basic helix-loop-helix domain containing, class B2 mRNAs exhibited a clear increase after 3- and 24-h treatment. The guanine-nucleotide exchange factor RalGDS was greatly up-regulated after 3-h treatment but not 24 h after. The results suggest an early involvement of these genes in T3 action during neuroblastoma cell differentiation probably mediating later changes in gene expression pattern.
甲状腺激素早已被证实能调节神经发育。妊娠期和产后早期的甲状腺功能减退会导致严重的神经后果，甚至包括智力迟钝。本研究旨在描述甲状腺激素诱导神经-2aβ细胞分化过程中的基因表达模式，以便选择“直接反应基因”进行进一步分析。在这种神经母细胞瘤细胞系中，甲状腺激素可阻止增殖并诱导分化。用 cDNA 芯片检测 T3 处理 3 和 24 h 后基因表达水平的变化。T3 处理后有 16 个基因显著上调，79 个基因下调。有 5 个上调基因以前没有被描述为受甲状腺激素调节，由于它们对理解 T3 对细胞分化的作用具有潜在意义而被选中，通过 RT-PCR 分析进行了验证。转录因子 Phox2a 和碱性螺旋-环-螺旋结构域包含，B2 类 mRNA 在 3-和 24 h 处理后明显增加。鸟嘌呤核苷酸交换因子 RalGDS 在 3 h 处理后大大上调，但在 24 h 后没有上调。结果表明，这些基因在神经母细胞瘤细胞分化过程中，可能介导了基因表达模式的后期变化，可能在 T3 作用中早期参与。
