Caspase mRNA expression in a rat model of focal cerebral ischemia
Caspase mRNA expression in a rat model of focal cerebral ischemia
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DOI：
10.1016/s0169-328x(01)00058-4
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发表时间：
2001-04-18
期刊：
影响因子：
--
通讯作者：
Philpott, KL
中科院分区：
文献类型：
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作者：
Harrison, DC;Davis, RP;Philpott, KL
Caspase家族的蛋白参与了最终导致细胞程序性死亡(细胞凋亡)的信号通路，据报道，这种死亡发生在一些中风的实验模型中。在之前的一篇论文中，我们使用定量逆转录和聚合酶链式反应(RT-PCR)来表征该家族成员caspase-3的mRNA表达的变化。在永久性局灶性缺血的大鼠模型中。在这里，我们使用这一技术来研究另外三个半胱氨酸酶的表达，它们涉及到半胱氨酸酶信号的不同方面。Caspase-8参与Fas介导的细胞凋亡，在缺血大鼠大脑皮质表达上调。Caspase-11，导致细胞因子IL-1β的功能性形式的合成。也显示表达增加，但与caspase-8的时间分布不同。相比之下，caspase-9是通过线粒体发出信号的途径的一部分。表现出表达的减少。另外四个半胱氨酸酶(1、2、6和7)的表达也在一个更简单的实验中得到了表征。这些半胱氨酸天冬氨酸氨基转移酶在诱导缺血后均表现出不同的表达模式。这些数据使我们得出结论，在这个模型中，caspase的表达作为一个整体受到非常严格的转录控制。Caspase信号的某些元件，如Fas诱导的通路和IL-1β处理的上游事件，上调，而其他元件则不上调。这可能是由于某种形式的遗传程序被激活，以响应大脑中的缺血，并可能突出哪些生物途径受到调节。(C)2001 Elsevier Science B.V.保留所有权利。
Proteins of the caspase family are involved in the signalling pathway that ultimately leads to programmed cell death (apoptosis), which has been reported to occur in some experimental models of stroke. In a previous paper we used quantitative reverse transcription and polymerase chain reaction (RT-PCR) to characterise changes in the mRNA expression of one member of this family, caspase-3. in a rat model of permanent focal ischemia. Here we have used this technique to study the expression of a further three caspases which are involved in different aspects of caspase signalling. Caspase-8, involved in Fas-mediated apoptosis, was upregulated in the cortex of ischemic rats. Caspase-11, which leads to the synthesis of the functional form of the cytokine interleukin-1 beta. also showed increased expression, but with a different temporal profile From caspase-8. In contrast, caspase-9, which forms part of the pathway signalling through the mitochondria. showed a decrease in expression. The expression of a further four caspases (1, 2, 6 and 7) has also been characterised in a simpler experiment. These caspases all showed distinctive patterns of expression following the induction of ischemia. These data lead us to conclude that caspase expression as a whole is under very strict transcriptional control in this model. Certain elements of caspase signalling, such as the Fas-induced pathway and the events upstream of IL-1 beta processing, are upregulated, while others are not. This may be due to some form of genetic program activated in response to ischemia in the brain and may highlight which biological pathways are modulated. (C) 2001 Elsevier Science B.V. All rights reserved.