Erhardt Nola M, Haines Lee R, Pearson Terry W, Sherwood Nancy M
Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
J Mol Neurosci. 2005;27(1):107-23. doi: 10.1385/JMN:27:1:107.
We showed previously that early chick neuroblasts stop proliferating and undergo apoptosis when deprived of endogenous pituitary adenylate cyclase-activating polypeptide (PACAP). To identify proteins involved in these processes, we blocked the primary PACAP receptor and determined protein changes using isotope-coded affinity tag (ICAT) analysis. Cell cycle exit was characterized by a decrease in proteins regulating ribosome biogenesis and protein translation. Apoptosis was linked directly to a tumor suppressor that increases apoptosome activity and indirectly to reduced mitochondrial activity. ICAT analysis, combined with flow cytometric analysis, suggested that some cells were differentiating, rather than undergoing apoptosis. In summary, we have confirmed that withdrawal of PACAP from early chick neuroblasts causes cell cycle exit and apoptosis, and identified proteins involved in proliferation, exit, apoptosis, and possibly differentiation.
我们之前表明，早期鸡胚神经母细胞在缺乏内源性垂体腺苷酸环化酶激活多肽（PACAP）时会停止增殖并发生凋亡。为了鉴定参与这些过程的蛋白质，我们阻断了主要的PACAP受体，并使用同位素编码亲和标签（ICAT）分析来确定蛋白质的变化。细胞周期退出的特征是调节核糖体生物合成和蛋白质翻译的蛋白质减少。凋亡直接与一种增加凋亡小体活性的肿瘤抑制因子相关，间接与线粒体活性降低相关。ICAT分析与流式细胞术分析相结合表明，一些细胞正在分化，而不是发生凋亡。总之，我们已经证实，从早期鸡胚神经母细胞中去除PACAP会导致细胞周期退出和凋亡，并鉴定出参与增殖、退出、凋亡以及可能的分化过程的蛋白质。
