Hypothalamic and amygdalar cell lines differ markedly in mitochondrial rather than nuclear encoded gene expression.

Hypothalamic and amygdalar cell lines differ markedly in mitochondrial rather than nuclear encoded gene expression.
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DOI:
10.1186/1471-2164-14-413
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发表时间:
2013-06-21
期刊:
影响因子:
4.4
通讯作者:
Uht RM
Uht RM
中科院分区:
生物学2区
文献类型:
--
作者:
Dalwadi DA;Uht RM

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促肾上腺皮质激素释放激素(CRH)在调节哺乳动物应激反应中起重要作用。两个最广泛研究的表达CRH的神经元群体位于下丘脑和杏仁核。这两个区域都参与压力反应,但杏仁核也参与调节对恐惧和焦虑的反应。考虑到下丘脑和杏仁核具有重叠的功能,但它们的CRH表达神经元可能对给定的扰动有不同的反应,我们试图确定两种神经元细胞类型(杏仁AR-5和下丘脑IVB细胞)之间差异表达的基因。因此,我们进行了微阵列分析。我们的假设是,我们将确定差异表达的转录因子,辅调节和染色质修饰酶。共分析了31,042个基因,其中10,572个在95%置信水平下在两种细胞系中一致表达。在10,572个基因中,AR-5中有2,320个基因的表达水平相对于IVB ≥ 2倍,IVB中有1,104个基因的表达水平相对于AR-5 ≥2倍,两种细胞系中有7,148个基因的表达水平相似。最大的差异是在六个线粒体DNA编码的基因,这是非常丰富的AR-5相对于IVB细胞。根据微阵列结果,这些基因的相对丰度范围为413至885倍。通过RTqPCR验证这些基因的差异表达。差异表达的线粒体基因为细胞色素B(MT-CYB)、细胞色素c氧化酶亚基1和2(MT-CO 1和MT-CO 2)以及NADH-泛醌氧化还原酶链1、2和3(MT-ND 1、MT-ND 2、MT-ND 3)。正如预期的那样,该阵列揭示了转录因子和辅助调节因子的差异表达;然而,两种细胞系之间的最大差异在于由线粒体基因组编码的基因。这些基因在AR-5中相对于IVB是丰富的。目前,造成这种显著差异的原因尚不清楚。这些细胞可能在mtDNA拷贝数、线粒体数量或线粒体基因组调控方面存在差异。具有这种不同水平的线粒体表达所起的具体作用尚未确定。可能杏仁核细胞中线粒体基因的更高表达反映了比下丘脑细胞系中更高的能量需求。
Corticotropin-releasing hormone (CRH) plays an important role in regulating the mammalian stress response. Two of the most extensively studied neuronal populations that express CRH are in the hypothalamus and amygdala. Both regions are involved in the stress response, but the amygdala is also involved in mediating response to fear and anxiety. Given that both hypothalamus and amygdala have overlapping functions, but their CRH-expressing neurons may respond differently to a given perturbation, we sought to identify differentially expressed genes between two neuronal cell types, amygdalar AR-5 and hypothalamic IVB cells. Thus, we performed a microarray analysis. Our hypothesis was that we would identify differentially expressed transcription factors, coregulators and chromatin-modifying enzymes. A total of 31,042 genes were analyzed, 10,572 of which were consistently expressed in both cell lines at a 95% confidence level. Of the 10,572 genes, 2,320 genes in AR-5 were expressed at ≥ 2-fold relative to IVBs, 1,104 genes were expressed at ≥2-fold in IVB relative to AR-5 and 7,148 genes were expressed at similar levels between the two cell lines. The greatest difference was in six mitochondrial DNA-encoded genes, which were highly abundant in AR-5 relative to IVB cells. The relative abundance of these genes ranged from 413 to 885-fold according to the microarray results. Differential expression of these genes was verified by RTqPCR. The differentially expressed mitochondrial genes were cytochrome b (MT-CYB), cytochrome c oxidase subunit 1 and 2 (MT-CO1 and MT-CO2) and NADH-ubiquinone oxidoreductase chain 1, 2, and 3 (MT-ND1, MT-ND2, MT-ND3). As expected, the array revealed differential expression of transcription factors and coregulators; however the greatest difference between the two cell lines was in genes encoded by the mitochondrial genome. These genes were abundant in AR-5 relative to IVBs. At present, the reason for the marked difference is unclear. The cells may differ in mtDNA copy number, number of mitochondria, or regulation of the mitochondrial genome. The specific functions served by having such different levels of mitochondrial expression have not been determined. It is possible that the greater expression of the mitochondrial genes in the amygdalar cells reflects higher energy requirements than in the hypothalamic cell line.
DOI: 10.1093/nar/gkn760
发表时间: 2009-01
影响因子: 14.9
作者:
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
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DOI: 10.1210/en.140.1.251
发表时间: 1999-01-01
期刊: ENDOCRINOLOGY
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发表时间: 1977-01-01
影响因子: 3.9
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发表时间: 2005-07-01
影响因子: 3.4
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通讯作者: Van Bockstaele, EJ