Zoref-Shani E, Bromberg Y, Lilling G, Gozes I, Brosh S, Sidi Y, Sperling O
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Int J Dev Neurosci. 1995 Dec;13(8):887-96. doi: 10.1016/0736-5748(95)00054-2.
The present study was conducted in order to clarify the role of the glia in brain purine metabolism. This, in connection with the clarification of the etiology of the neurological manifestations associated with some of the inborn errors of purine metabolism in man. Purine nucleotide content, the capacity for de novo and salvage purine synthesis and the activity of several enzymes of purine nucleotide degradation, were assayed in primary cultures of rat astroglia in relation to culture age. The capacity of the intact cells to produce purine nucleotides de novo exhibited a marked decrease with the culture age, but the activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), catalyzing salvage nucleotide synthesis, increased. Aging was also associated with a marked increase in the activity of the degradation enzymes AMP deaminase, purine nucleoside phosphorylase (PNP) and guanine deaminase (guanase). The activity of adenosine deaminase and of AMP-5'-nucleotidase, increased markedly during the first 17 days in culture, but decreased thereafter. The results indicate that purine nucleotide metabolism in the cultured astroglia is changing with aging to allow the cells to maintain their nucleotide pool by reutilization of preformed hypoxanthine, rather than by de-novo production of new purines. Aging is also associated with increased capacity for operation of the adenine nucleotide cycle, contributing to the homeostasis of adenine nucleotides and to the energy charge of the cells. In principle, the age-related alterations in purine metabolism in the astroglia resemble those occurring in the maturating neurons, except for the capacity to produce purines de novo, which exhibited inverse trends in the two tissues. However, in comparison to the neurons, the cultured astroglia possess the capacity for a more intensive metabolism of purine nucleotides.
本研究旨在阐明神经胶质细胞在脑嘌呤代谢中的作用。这与阐明人类某些嘌呤代谢先天性缺陷相关神经学表现的病因有关。在大鼠星形胶质细胞原代培养物中，检测了嘌呤核苷酸含量、从头合成和补救合成嘌呤的能力以及几种嘌呤核苷酸降解酶的活性，并与培养年龄相关联。完整细胞从头合成嘌呤核苷酸的能力随培养年龄的增加而显著降低，但催化补救核苷酸合成的次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HGPRT）的活性增加。衰老还与降解酶AMP脱氨酶、嘌呤核苷磷酸化酶（PNP）和鸟嘌呤脱氨酶（鸟苷酶）的活性显著增加有关。腺苷脱氨酶和AMP - 5'-核苷酸酶的活性在培养的前17天显著增加，但此后降低。结果表明，培养的星形胶质细胞中的嘌呤核苷酸代谢随衰老而变化，使细胞能够通过重新利用预先形成的次黄嘌呤来维持其核苷酸池，而不是通过从头合成新的嘌呤。衰老还与腺嘌呤核苷酸循环运作能力的增加有关，有助于腺嘌呤核苷酸的稳态和细胞的能量电荷。原则上，星形胶质细胞中与年龄相关的嘌呤代谢变化类似于成熟神经元中发生的变化，除了从头合成嘌呤的能力，这在两种组织中呈现相反的趋势。然而，与神经元相比，培养的星形胶质细胞具有更强的嘌呤核苷酸代谢能力。
