Zhou An, Simon Roger P, David Larry
Neuroscience Institute, Morehouse School of Medicine, 720 Westview Dr SW, Atlanta, GA 30310, USA.
Int J Comput Biol Drug Des. 2011;4(1):40-55. doi: 10.1504/IJCBDD.2011.038656. Epub 2011 Feb 17.
In a recent study on ischemic rodent brains, we quantitatively characterised and compared brain proteomes under ischemic-preconditioned or injured or tolerant conditions. We discovered an enriched presence of repressive transcriptional regulator proteins with essential roles as epigenetic regulators in ischemic-tolerant brains (Stapels et al., 2010). We further showed their robust, dynamic and differential changes under different ischemic conditions in brains and in cultured neuronal cells. In the present work, using neuronal cell cultures, we aimed to characterise the nascent proteome, the proteome that presents early when the cells receive an ischemic insult. These would be the proteomic changes of newly synthesised proteins. Identification of effectors of this phase of response to ischemia bears the best promise of identifying therapeutic targets for treating acute stroke when patients present to hospital. We compared these nascent proteomes across different ischemic conditions using bioinformatic tools.
在最近一项针对缺血性啮齿动物大脑的研究中,我们对缺血预处理、损伤或耐受条件下的大脑蛋白质组进行了定量表征和比较。我们发现,在缺血耐受的大脑中,作为表观遗传调节因子发挥重要作用的抑制性转录调节蛋白含量丰富(斯特佩斯等人,2010年)。我们进一步展示了它们在大脑和培养的神经元细胞中不同缺血条件下的强烈、动态和差异性变化。在本研究中,我们利用神经元细胞培养来表征新生蛋白质组,即细胞受到缺血损伤后早期出现的蛋白质组。这些将是新合成蛋白质的蛋白质组学变化。确定缺血反应这一阶段的效应因子,最有希望找到治疗急性中风患者的治疗靶点。我们使用生物信息学工具比较了不同缺血条件下的这些新生蛋白质组。