Global ischemia induces immediate-early genes encoding zinc finger transcription factors
Global ischemia induces immediate-early genes encoding zinc finger transcription factors
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DOI：
10.1097/00004647-199607000-00005
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发表时间：
1996-07-01
影响因子：
6.3
通讯作者：
Sharp, FR
中科院分区：
文献类型：
--
作者：
Honkaniemi, J;Sharp, FR
缺血会在大脑中诱导即早基因（IEG）。由于某些 IEG 的长时间表达可能先于神经元死亡，因此一些研究人员认为这些 IEG 介导了神经元死亡。因此，我们检查了 5 分钟和 10 分钟的整体缺血对沙鼠脑中 IEG NGFI-A、NGFI-B、NGFI-C、egr-2、egr-3 和 Nurr1 表达的影响。所有 IEG 均在海马再灌注 30 分钟后诱导。其中大多数也在其他几个区域被诱导，包括皮质、下丘脑、丘脑和杏仁核。大多数大脑区域的急性 IEG 诱导减少 2-6 小时。然而，在缺血 5 分钟后的 24 小时，NGFI-A 继续在 CA1 区和齿状回表达。在齿状回中，NGFI-C 持续表达 24 小时，egr-3 持续表达长达 72 小时。在其他大脑区域，所有 IEG 在 72 小时后恢复到控制水平，但 CA1 除外，其中大多数信使 RNA (mRNA) 水平下降；这种减少与显着的神经元损失相关。 NGFI-A 在注定死亡的 CA1 神经元中持续表达，以及 NGFI-A、NGFI-C 和 egr-3 基因在存活的齿状颗粒细胞神经元中持续表达，可能表明一些转录因子调节细胞死亡，而另一些转录因子在长时间表达时支持细胞存活。已知包括 c-fos 在内的几种转录因子的蛋白质产物会下调其自身表达。因此，注定死亡的 CA1 神经元中 NGFI-A 的持续表达可能是由于缺血引起的转录激活，例如细胞内钙水平增加，加上 NGFI-A mRNA 翻译成蛋白质的阻断导致负反馈的缺乏。
Ischemia induces immediate-early genes (IEGs) in brain. Since prolonged expression of some IEGs may precede neuronal death, some researchers have suggested that these IEGs mediate neuronal death. We therefore examined the effect of 5 and 10 min of global ischemia on the expression of the IEGs NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 in gerbil brain. All of the IEGs were induced after 30 min of reperfusion in the hippocampus. Most of them were induced in several other regions as well, including cortex, hypothalamus, thalamus, and amygdala. The acute IEG induction decreased in most brain areas by 2-6 h. However, at 24 h following 5 min of ischemia NGFI-A continued to be expressed in the CA1 region and dentate gyrus. In the dentate gyrus, NGFI-C continued to be expressed for 24 h and egr-3 for as long as 72 h. In other brain areas, all of the IEGs returned to control levels by 72 h except in CA1, where most messenger RNA (mRNA) levels were decreased; this decrease correlated with marked neuronal loss. The persistent expression of NGFI-A in CA1 neurons destined to die and the persistent expression of NGFI-A, NGFI-C, and egr-3 genes in dentate granule cell neurons that survive may indicate that some transcription factors modulate cell death whereas others support cell survival when expressed for prolonged periods, The protein products of several transcription factors, including c-fos, are known To downregulate their own expression. The persistent expression of NGFI-A in the CA1 neurons destined to die could therefore be due to ischemia-induced transcriptional activation caused by, e.g., increased intracellular calcium levels plus a lack of negative feedback caused by the blockade of the translation of NGFI-A mRNA into protein.