Methods for the study of purine metabolism in human cells in vitro

Henderson, J. Frank; Fraser, Joyce H.; McCoy, Ernest E.

doi:10.1016/s0009-9120(74)92842-2

Cited by 61 publications

(17 citation statements)

References 27 publications

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“…3). Similarly, acadesine also inhibited unstimulated and stimulated neutrophil adherence to fibroblasts (EC50, 13 ,uM and 18 ,uM, respectively, P < 0.001; Fig. 4) at concentrations similar to those required for promotion of adenosine release.…”

Section: Resultsmentioning

confidence: 67%

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

Cronstein

Eberle

Gruber

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

314

158

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(IC50, 9 nM) and stimulated neutrophils (IC5*, 13 nM). Methotrexate treatment inhibited neutrophil adherence by enhing adenosine release from fibroblasts since digestion of extracellular adenosine by added adenosine deaminase completely abrogated the effect ofmethotrexate on neutrophil adherence without, itself, affecting adherence. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibiton of 5-aminoimidazole-

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Section: Resultsmentioning

confidence: 67%

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

Cronstein

Eberle

Gruber

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

314

158

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“…Decline in the intracellular ATP pool is consistent with mitigation of OxPhos by the drug (42,43). Decrease in other NTP pools suggest that overall energy metabolism is affected by inhibiting PI3K pathway (Figure 5E).…”

Section: Discussionmentioning

confidence: 70%

B-cell Receptor Signaling Regulates Metabolism in Chronic Lymphocytic Leukemia

Vangapandu

Havránek

Ayres

et al. 2017

Molecular Cancer Research

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Chronic lymphocytic leukemia (CLL) cells are quiescent but have active transcription and translation processes, suggesting that these lymphocytes are metabolically active. Based on this premise, the metabolic phenotype of CLL lymphocytes was investigated by evaluating the two intracellular ATP generating pathways. Metabolic flux was assessed by measuring glycolysis as extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation as oxygen consumption rate (OCR) and then correlated with prognostic factors. Further, the impact of B-cell receptor signaling (BCR) on metabolism was determined by genetic ablation and pharmacological inhibitors. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in CLL cells. ECAR was consistently low, but OCR varied considerably in human patient samples (n=45). Higher OCR was associated with poor prognostic factors such as ZAP70 positivity, unmutated IGHV, high β2M levels, and higher Rai stage. Consistent with the association of ZAP70 and IGHV unmutated status with active BCR signaling, genetic ablation of BCR mitigated OCR in malignant B-cells. Similarly, knocking out PI3Kδ, a critical component of the BCR pathway, decreased OCR and ECAR. In concert, PI3K pathway inhibitors, dramatically reduced OCR and ECAR. In harmony with a decline in metabolomics, the ribonucleotide pools in CLL cells were reduced with duvelisib treatment. Collectively, these data demonstrate that CLL metabolism, especially OCR, is linked to prognostic factors and is curbed by BCR and PI3K pathway inhibition.

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“…The rapid incorporation of guanosine into guanine nucleotides of erythrocytes is well known due to the work of Brown et al [4], Kong and Parks [22], Henderson et al [19,20] and from an earlier study carried out in our laboratory [5], The present investigatin provides, however, more detailed infor mation about the effect of pH and concen tration of inorganic phosphate and guano sine. The experimental design with contin uous addition and removal of substances through a dialysis system gave unique possi bilities to study the metabolic reaction and their substance rates at physiologically low concentrations.…”

Section: Discussionmentioning

confidence: 62%

“…Previous investigations of guanine/guanosine metabolism in human erythrocytes are not systematic [4,19] and do not give good estimates of the metabolic fluxes under conditions normally prevailing in the eryth rocytes, i.e. with purine and nucleoside con centrations around 1 pmol • l"1 and phos phate concentration around 1 mmol -1"1.…”

Section: Introductionmentioning

confidence: 96%

Metabolism of Guanosine in Human Erythrocytes

Ericson¹,

Niklasson²,

Verdier³

1985

Vox Sanguinis

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The metabolism of guanosine in human erythrocytes has been studied in two different experimental systems - direct incubation and dialysis incubation - the latter allowing continuous addition and removal of substances. Intra- and extracellular purine compounds were analyzed using high-performance liquid chromatography (HPLC). At 37 °C, a normal pH (7.4) and a favorably high concentration of inorganic phosphate, guanine nucleotides were synthesized at a substance rate of about 0.17 mmol • h^-1 (calculated per liter erythrocytes) when guanosine was kept at a concentration of 25 µmol • l^-1. At a higher guanosine concentration the rate of synthesis increased only moderately. Erythrocytes loaded with guanylates lost these nucleotides at a rate of 0.023 mmol • h^-1 at a normal phosphate concentration and somewhat slowlier at a higher phosphate concentration. The metabolism kept the guanylates in an equilibrium that was similar to the equilibrium between the adenylates.

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Methods for the study of purine metabolism in human cells in vitro

Cited by 61 publications

References 27 publications

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

B-cell Receptor Signaling Regulates Metabolism in Chronic Lymphocytic Leukemia

Metabolism of Guanosine in Human Erythrocytes

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