The purine metabolism of human erythrocytes

Dudzińska, Wioleta; Hlynczak, A.J.; Skotnicka, E.; Suska, M.

doi:10.1134/s0006297906050014

Cited by 32 publications

(43 citation statements)

References 72 publications

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“…by Swiss-Prot) to extracellular space. Although minor endothelial cell contamination cannot be excluded, RBCs express a phosphoribosyl-pyrophosphate synthetase (56). In other cells (57) these complex with phosphoribosyl-pyrophosphate synthetase-associated protein, suggesting that similar association may occur in RBC membrane.…”

Section: Comparative Analysis Of Mouse and Human Rbc Proteomesmentioning

confidence: 99%

Deep Coverage Mouse Red Blood Cell Proteome

Pasini

Kirkegaard

Salerno

et al. 2008

Molecular & Cellular Proteomics

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Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much research has therefore focused on RBC and cardiovascular disorders of mouse and humans. RBCs also host malaria parasites. Recently we presented an in-depth proteome for the human RBC. Here we present directly comparable data for the mouse RBC as membrane-only, soluble-only, and combined membranebound/soluble proteomes (comprising, respectively, 247, 232, and 165 proteins). All proteins were identified, validated, and categorized in terms of subcellular localization, protein family, and function, and in comparison with the human RBC, were classified as orthologs, family-related, or unique. Splice isoforms were identified, and polypeptides migrating with anomalous apparent molecular weights were grouped into putatively ubiquitinated or partially degraded complexes. Overall there was close concordance between mouse and human proteomes, confirming the unexpected RBC complexity. Several novel findings in the human proteome have been confirmed here. This comparison sheds light on several open issues in RBC biology and provides a departure point for more comprehensive understanding of RBC function.

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Section: Comparative Analysis Of Mouse and Human Rbc Proteomesmentioning

confidence: 99%

Deep Coverage Mouse Red Blood Cell Proteome

Pasini

Kirkegaard

Salerno

et al. 2008

Molecular & Cellular Proteomics

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“…For example, a 9-mL sample of EDTA blood from an adult contains around 5 ϫ 10 10 red blood cells, 3 ϫ 10 9 platelets, and 8 ϫ 10 7 leukocytes. Hypoxanthine is a final product of adenosine monophosphate and inosine monophosphate catabolism that reaches the plasma by diffusion (27 ). S-1-P can be released by platelets (28 ) and erythrocytes (29 ).…”

Section: Fig 4 Impact Of Placing Freshly Drawn Blood In Ice Water Fmentioning

confidence: 99%

Preanalytical Aspects and Sample Quality Assessment in Metabolomics Studies of Human Blood

et al. 2013

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“…Indeed, despite previous studies of natural nucleoside metabolism in RBC (10,32), little is known about intracellular deoxynucleotide triphosphates except their low concentrations (e.g., that of dATP is Ͻ0.1 pmol/10 6 normal RBC [7]). Note that RBC are known for their inability to synthesize purine nucleotides in the de novo pathway (10), which enables a unique nucleotide equilibrium to develop in RBC.…”

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confidence: 99%

“…Note that RBC are known for their inability to synthesize purine nucleotides in the de novo pathway (10), which enables a unique nucleotide equilibrium to develop in RBC.…”

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confidence: 99%

Evidence and Possible Consequences of the Phosphorylation of Nucleoside Reverse Transcriptase Inhibitors in Human Red Blood Cells

Durand-Gasselin

Silva

Bénech

et al. 2007

Antimicrob Agents Chemother

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The intracellular metabolism of nucleoside reverse transcriptase inhibitors (NRTI) in mononuclear cells has been thoroughly studied, but that in red blood cells (RBC) has been disregarded. However, the phosphorylation of other analogous nucleosides (in particular, ribavirin) has been described previously. In this study, we investigated for the first time the phosphorylation of NRTI in human RBC. The presence of intracellular zidovudine (AZT) monophosphate, AZT triphosphate, lamivudine (3TC) triphosphate, and tenofovir (TFV) diphosphate, as well as endogenous dATP, dGTP, and dTTP, in RBC collected from human immunodeficiency virus-infected patients was examined. We observed evidence of a selective phosphorylation of 3TC, TFV, and endogenous purine deoxynucleosides to generate their triphosphate moieties. Conversely, no trace of AZT phosphate metabolites was found, and only faint dTTP signals were visible. A comparison of intracellular TFV diphosphate and 3TC triphosphate levels in RBC and peripheral blood mononuclear cells (PBMC) further highlighted the specificity of NRTI metabolism in each cell type. These findings raise the issue of RBC involvement in drug-drug interaction, drug pharmacokinetics, and drug-induced toxicity. Moreover, the typical preparation of PBMC samples by gradient density centrifugation does not prevent their contamination with RBC. We demonstrated that the presence of RBC within PBMC hampers an accurate determination of intracellular TFV diphosphate and dATP levels in clinical PBMC samples. Thus, we recommend removing RBC during PBMC preparation by using an ammonium chloride solution to enhance both the accuracy and the precision of intracellular drug monitoring.Nucleoside reverse transcriptase inhibitors (NRTI) constitute a peculiar category of antiretroviral drugs because they undergo multistep intracellular activation to exert the antiviral activity through the corresponding triphosphate, NRTI-TP. In fact, both the NRTI antiretroviral effect (13,14,18,34) and mitochondrial toxicity (12) are related to the intracellular metabolism of NRTI. To date, intracellular pharmacological studies of patients have been focused on peripheral blood mononuclear cells (PBMC). These cells are the primary targets of human immunodeficiency virus (HIV) and are readily available from a single blood sample of around 7 ml. Concentrations of NRTI-TP in PBMC (and/or the ratio of the level of NRTI-TP to that of the deoxynucleoside triphosphate [dNTP], the corresponding natural triphosphate) (18) are now regarded as relevant to investigations of new NRTI (24), drug-drug interaction studies (9,15,17,22,27), and prescription strategies (33, 35). On the other hand, few studies (30) have addressed the role of NRTI phosphate concentrations in drug toxicity or in the persistence of virus in protected areas. Such investigations should be performed with different cell types (e.g., red blood cells [RBC], lymphocyte node mononuclear cells, adipocytes, and muscle cells), which are often difficult to collect from patients in ...

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The purine metabolism of human erythrocytes

Cited by 32 publications

References 72 publications

Deep Coverage Mouse Red Blood Cell Proteome

Deep Coverage Mouse Red Blood Cell Proteome

Preanalytical Aspects and Sample Quality Assessment in Metabolomics Studies of Human Blood

Evidence and Possible Consequences of the Phosphorylation of Nucleoside Reverse Transcriptase Inhibitors in Human Red Blood Cells

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