Incorporation of purine nucleosides in cultured fibroblasts from a patient with purine nucleoside phosphorylase deficiency and associated T‐cell immunodeficiency

Burke, Wynn; Chen, Shi‐Han; Scott, C. Ronald; Ammann, Arthur J.

doi:10.1002/jcp.1040920113

Cited by 11 publications

(1 citation statement)

References 9 publications

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“…Xanthine and uric acid, which are also catabolic products of xanthosine and XMP, are not substrates for HGPRT (Harkness et al, 19901, and 8-bromo-inosine is not a substrate for PNP (Bzowska et al, 1988). Direct phophorylation of xanthosine, 8-bromo-inosine, or inosine to the nucleotide level would be unlikely because kinases for these nucleosides cannot be demonstrated in cell cultures of other vertebrates (Friedmann et al, 1969;Burke et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of proliferation in cultures of Chinook salmon embryo cells by interactions between inosine and bovine sera

Ganassin

Tran

Rabgey

et al. 1994

Journal Cellular Physiology

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The influence of inosine on DNA synthesis by Chinook salmon embryo cells (CHSE-214) was investigated because previously cell number was shown to increase from six- to thirtyfold if inosine was added to the basal medium (L-15) supplemented with either dialyzed fetal bovine serum (dFBS), calf serum (CS), or dCS. Relative to L-15, 3H-thymidine incorporation was inhibited by these sera alone but elevated in nondialyzed (intact) FBS. Inosine at 10 microM stimulated 3H-thymidine incorporation from ten- to seventyfold in dFBS, CS, and dCS but was only slightly stimulatory in FBS and in L-15 alone. As well as inosine, hypoxanthine, cIMP, IMP, IDP, and ITP were just as stimulatory, but the nonsalvageable purines (xanthine, xanthosine, and XMP) were not. The stimulatory action of inosine was highest in low density cultures. Dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), inhibitors of facilitated nonconcentrative nucleoside transport, did not completely block the enhancement of cell number by inosine and by themselves increased proliferation in CS and dCS. Overall, these results suggest that exogenous inosine promoted CHSE-214 proliferation by overcoming factors in the nondialyzable fraction of sera that led to purine loss and by raising intracellular purine nucleotides to levels necessary for cells to respond to growth factors in the nondialyzable fraction of sera.

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Section: Discussionmentioning

confidence: 99%

Enhancement of proliferation in cultures of Chinook salmon embryo cells by interactions between inosine and bovine sera

Ganassin

Tran

Rabgey

et al. 1994

Journal Cellular Physiology

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Adenosine transport and metabolism in mouse leukemia cells and in canine thymocytes and peripheral blood leukocytes

Lum

März

Plagemann

et al. 1979

Journal Cellular Physiology

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The intracellular accumulation of free 13H1 adenosine was measured by rapid kinetic techniques in P388 murine leukemia cells in which adenosine metabolism (phosphorylation and deamination) was completely prevented by depletion of cellular ATP and by treatment with deoxycoformycin. Nonlinear regression of integrated rate equations on the data demonstrate that the time courses of labeled adenosine accumulation at various extracellular adenosine concentrations in zero-trans and equilibrium exchange protocols are well described by a simple, completely symmetrical, transport model with a carrier:substrate affinity constant of about 150 pM. Adenosine transport was not affected by 1 mM deoxycoformycin indicating that this analog has a low affinity for the nucleoside transport system. The transport capacity of dog thymocytes and peripheral leukocytes was similar to that of P388 cells. Transport was not inhibited by deoxycoformycin and remained constant during the first two hours after mitogenic stimulation with concanavalin A. In untreated, metabolizing P388 cells transport was found to be the major determinant of the rate of intracellular metabolism, regardless of the extracellular adenosine concentration (up to a t least 160 pM), but the long-term accumulation (longer than 30-60 seconds) of radioactivity from extracellular adenosine strictly reflected the rate of formation of nucleotides (mainly ATP). The metabolism of adenosine by whole cells was entirely consistent with the kinetic properties of the transport system and those of the metabolic enzymes.At low exogenous adenosine concentrations (1 pM and below) transport was slow enough to allow direct phosphorylation of most of the entering adenosine. The remainder was deaminated and rapidly converted to nucleotides via inosine, hypoxanthine, and IMP. At concentrations of 100 p M or higher, on the other hand, influx exceeded the maximum velocity of adenosine kinase about 100 times so that most of the entering adenosine was deaminated. But since the maximum velocity of adenosine deaminase exceeded those of nucleoside phosphorylase and hypoxanthinelguanine phosphoribosyltransferase about 5 and 100 times, respectively, hypoxanthine and inosine rapidly exited from the cells and accumulated in the medium. A 98% reduction of adenosine transport (at 100 pM), caused by the transport inhibitor Persantin, inhibited adenosine deamination by whole cells to about the same extent as transport, whereas adenosine phosphorylation was relatively little affected; thus in the presence of Persantin, transport and metabolism resembled that occurring at the low adenosine concentration. These and other results indicate that adenosine deamination is an event distinct from transport, which occurs only subsequent to adenosine's transport into the cell.

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Disorders of Purine and Pyrimidine Metabolism

Seegmiller

1979

Contemporary Metabolism

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Incorporation of purine nucleosides in cultured fibroblasts from a patient with purine nucleoside phosphorylase deficiency and associated T‐cell immunodeficiency

Cited by 11 publications

References 9 publications

Enhancement of proliferation in cultures of Chinook salmon embryo cells by interactions between inosine and bovine sera

Enhancement of proliferation in cultures of Chinook salmon embryo cells by interactions between inosine and bovine sera

Adenosine transport and metabolism in mouse leukemia cells and in canine thymocytes and peripheral blood leukocytes

Disorders of Purine and Pyrimidine Metabolism

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