Maino Barbara, Ciotti Maria Teresa, Calissano Pietro, Cavallaro Sebastiano
Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95126 Catania, Italy.
European Brain Research Institute, Via del Fosso di Fiorano 64, 00143 Roma, Italy.
Int J Mol Sci. 2014 Apr 1;15(4):5596-622. doi: 10.3390/ijms15045596.
Apoptosis triggered by exogenous or endogenous stimuli is a crucial phenomenon to determine the fate of neurons, both in physiological and in pathological conditions. Our previous study established that gastric inhibitory polypeptide (Gip) is a neurotrophic factor capable of preventing apoptosis of cerebellar granule neurons (CGNs), during its pre-commitment phase. In the present study, we conducted whole-genome expression profiling to obtain a comprehensive view of the transcriptional program underlying the rescue effect of Gip in CGNs. By using DNA microarray technology, we identified 65 genes, we named survival related genes, whose expression is significantly de-regulated following Gip treatment. The expression levels of six transcripts were confirmed by real-time quantitative polymerase chain reaction. The proteins encoded by the survival related genes are functionally grouped in the following categories: signal transduction, transcription, cell cycle, chromatin remodeling, cell death, antioxidant activity, ubiquitination, metabolism and cytoskeletal organization. Our data outline that Gip supports CGNs rescue via a molecular framework, orchestrated by a wide spectrum of gene actors, which propagate survival signals and support neuronal viability.
由外源性或内源性刺激引发的细胞凋亡是在生理和病理条件下决定神经元命运的关键现象。我们之前的研究表明，胃抑制多肽（Gip）是一种神经营养因子，在小脑颗粒神经元（CGN）的预决定阶段能够预防其凋亡。在本研究中，我们进行了全基因组表达谱分析，以全面了解Gip对CGN的拯救作用背后的转录程序。通过使用DNA微阵列技术，我们鉴定出65个基因，我们将其命名为生存相关基因，其表达在Gip处理后显著失调。通过实时定量聚合酶链反应证实了六种转录本的表达水平。生存相关基因编码的蛋白质在功能上分为以下几类：信号转导、转录、细胞周期、染色质重塑、细胞死亡、抗氧化活性、泛素化、代谢和细胞骨架组织。我们的数据概述了Gip通过一个由广泛的基因参与者精心编排的分子框架来支持CGN的拯救，这些基因传播生存信号并支持神经元的活力。
