Elevated UTP and CTP content in cultured neurons from HPRT-deficient transgenic mice
Elevated UTP and CTP content in cultured neurons from HPRT-deficient transgenic mice
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DOI：
10.1385/jmn:14:1-2:087
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发表时间：
2000-02-01
影响因子：
3.1
通讯作者：
Zoref-Shani, E
中科院分区：
文献类型：
--
作者：
Brosh, S;Boer, P;Zoref-Shani, E
次黄嘌呤鸟嘌呤磷酸核糖转移酶(EC2.4.2.8.；HPRT)催化嘌呤碱次黄嘌呤和鸟嘌呤分别回收合成肌苷-5‘-一磷酸(IMP)和鸟苷-5’-一磷酸(GMP)。HPRT活性的完全缺乏与Lesch-Nyhan综合征(LNS)有关，LNS的特征是嘌呤产生过多和严重的神经系统症状。HPRT缺乏症的代谢后果的病因学已被阐明，但神经系统表现的病因学尚不清楚。HPRT缺陷小鼠是LNS的实验动物模型。为了寻找LNS大脑中可能的代谢异常，将神经缺陷与HPRT缺乏联系起来，现在测定了HPRT缺陷转基因小鼠的培养神经元的嘌呤和嘧啶核苷酸含量。Hprt基因缺陷的神经细胞培养中，嘧啶核苷酸UTP(是正常水平的1.33倍，p=0.0002)和CTP(是正常水平的1.28倍，p=0.02)显著升高，但嘌呤核苷酸三磷酸腺苷和谷丙转氨酶含量正常。这种神经元嘧啶核苷酸含量的异常可能与LNS神经功能障碍的病理生理机制有关。
Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8.; HPRT) catalyzes the salvage synthesis of inosine-5'-monophosphate (IMP) and guanosine-5'-monophosphate (GMP) from the purine bases hypoxanthine and guanine, respectively. Complete deficiency of HPRT activity is associated with the Lesch-Nyhan syndrome (LNS), characterized by excessive purine production and severe neurological manifestations. The etiology of the metabolic consequences of HPRT deficiency is clarified, but that of the neurological manifestations is not yet understood. HPRT-deficient mice represent an experimental animal model of LNS. In search for a possible metabolic abnormality in LNS brains, connecting the neurological deficit to HPRT deficiency, the purine and pyrimidine nucleotide content of cultured neurons, prepared from HPRT-deficient transgenic mice, was now determined. The HPRT-deficient neuronal cultures exhibited a significantly elevated content of the pyrimidine nucleotides UTP (1.33-fold the normal level, p = 0.0002) and CTP (1.28-fold the normal level, p = 0.02), but normal content of the purine nucleotides ATP and GTP. This abnormality in neuronal pyrimidine nucleotide content may be associated with the pathophysiology of the neurological deficit in LNS.