Purine metabolism during neuronal differentiation: the relevance of purine synthesis and recycling.
Purine metabolism during neuronal differentiation: the relevance of purine synthesis and recycling.
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DOI：
10.1111/jnc.12366
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发表时间：
2013-12
影响因子：
4.7
通讯作者：
Jinnah HA
中科院分区：
文献类型：
--
作者：
Göttle M;Burhenne H;Sutcliffe D;Jinnah HA
嘌呤是一类对所有细胞都至关重要的小有机分子。它们在神经元分化和功能中发挥关键作用。几种嘌呤代谢遗传性疾病凸显了它们的重要性，例如 Lesch-Nyhan 病，该病是由嘌呤补救酶次黄嘌呤鸟嘌呤磷酸核糖基转移酶 (HGprt) 缺乏引起的。尽管嘌呤在神经系统中的重要性众所周知，但有关其在神经元中代谢的知识仍然有限。在当前的研究中，在大鼠 PC6-3 细胞（一种 PC12 嗜铬细胞瘤亚克隆）中检查了嘌呤库及其代谢，该细胞在神经生长因子的作用下经历了强烈的分化。将结果与五个新的独立 PC6-3 亚克隆进行比较，这些亚克隆由于影响 HGprt 酶活性的不同突变而具有嘌呤回收缺陷。结果表明，神经元分化后大多数嘌呤和能量状态都会增加，并且当嘌呤循环丧失时会出现特定的异常。 HGprt 介导的嘌呤再循环的丧失也与突变型 PC6-3 系中多巴胺和相关代谢物的显着丧失相关，这表明嘌呤和多巴胺途径之间存在重要联系。这些结果提供了关于嘌呤池和代谢如何随着神经元分化而变化，以及特定酶缺陷如何导致神经元功能障碍的见解。
Purines are a class of small organic molecules that are essential for all cells. They play critical roles in neuronal differentiation and function. Their importance is highlighted by several inherited disorders of purine metabolism, such as the Lesch-Nyhan disease, which is caused by a deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Despite the known importance of purines in the nervous system, knowledge regarding their metabolism in neurons is limited. In the current studies, purine pools and their metabolism were examined in rat PC6-3 cells, a PC12 pheochromocytoma subclone that undergoes robust differentiation with nerve growth factor. The results were compared with five new independent PC6-3 subclones with defective purine recycling due to different mutations affecting HGprt enzyme activity. The results demonstrate an increase in most purines and in energy state following neuronal differentiation, as well as specific abnormalities when purine recycling is lost. The loss of HGprt-mediated purine recycling also is associated with significant loss of dopamine and related metabolites in the mutant PC6-3 lines, suggesting an important connection between purine and dopamine pathways. These results provide insights into how purine pools and metabolism change with neuronal differentiation, and how specific enzyme defects may cause neuronal dysfunction.
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影响因子：
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