Developmental changes in purine nucleotide metabolism in cultured rat astroglia.
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.
Zoref-Shani
E
E
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Bromberg
Y
Y
Lilling
G
G
Gozes
I
I
Brosh
S
S
Sidi
Y
Y
Sperling
O
O
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D002478:Cells, Cultured; D046508:Culture Techniques; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism*; D011687:Purines / Q000096:biosynthesis; D051381:Rats; D013997:Time Factors
D011685:Purine Nucleotides; D011687:Purines; D010754:Phosphoribosyl Pyrophosphate