Plasma purine nucleoside phosphorylase in cancer patients

Roberts, Elton L.; Newton, Russell P.; Axford, Alan T.

doi:10.1016/j.cccn.2004.02.008

Cited by 24 publications

(22 citation statements)

References 14 publications

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“…When quantified relative to IgM (loading control), the normalized intensity for upper immunoreactive band for NP was found to be significantly elevated in PDAC sera (n = 35, p<0.01, two-sided t-test using log-transformed data) compared to benign controls (n = 20, Figure 3F ), while it was undetectable in a subset of sera from other tumor types ( Figure S5 ). This predominance of NP expression in PDAC sera supported by an earlier report on its elevated enzyme activity in cancers [41] alluded to the possibility of finding altered levels of its target metabolites in serum of PDAC patients. Accordingly, levels of 7 metabolites namely adenine, adenosine, guanine, guanosine, xanthine, hypoxanthine and inosine which are either substrates or products of NP were measured in PDAC and benign sera using targeted LC-MS/MS.…”

Section: Resultssupporting

confidence: 56%

“…Importantly, as shown in Figure 2A , NP levels were higher in PDAC-associated juice compared to benign controls. The higher levels of this protein in PDAC combined with the earlier report on elevated NP activity in cancers [41], motivated us to evaluate this protein in PDAC tissues. As shown in Figure 3A , immunoblot analysis confirmed elevated expression of NP in PDAC tissues compared to benign specimens.…”

Section: Resultsmentioning

confidence: 99%

“…One of these was Purine Nucleoside Phosphorylase (NP), the rate limiting enzyme in salvage pathway involving purines, which is operational during inflammation as well as neoplastic progression, and has been highly targeted by various chemotherapeutic agents [61], [62], [63]. In cancers, NP activity has been previously reported to be high in cancer sera [41]. NP expression has also been used to determine the clinical severity of various types of leukemias and lymphomas especially as a ratio to adenosine deaminase (ADA)[64].…”

Section: Discussionmentioning

confidence: 99%

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Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

et al. 2011

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Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

et al. 2011

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“…), where their presence was generally ascribed to cell death or membrane alterations as a result of tissue damages or cancer (Brass and Mody ; Roberts et al . ).…”

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confidence: 97%

Evidence for purine nucleoside phosphorylase (PNP) release from rat C6 glioma cells

Giuliani

Zuccarini

Buccella

et al. 2017

Journal of Neurochemistry

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Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme. Cell exposure to 10 μM ATP or guanosine triphosphate (GTP) increased the extracellular amount of all corresponding purines without modifying the levels/activity of released PNP, whereas selective activation of ATP P2Y or adenosine A metabotropic receptors increased PNP release and purine base formation. The reduction to 1% in oxygen supply (2 h) to cells decreased the levels of released PNP, leading to an increased presence of extracellular nucleosides and to a reduced formation of xanthine and uric acid. Conversely, 2 h cell re-oxygenation enhanced the extracellular amounts of both PNP and purine bases. Thus, hypoxia and re-oxygenation modulated in opposite manner the PNP release/activity and, thereby, the extracellular formation of purine metabolism end-products. In conclusion, extracellular PNP and likely other enzymes deputed to purine base metabolism are released from cells, contributing to the purinergic system homeostasis and exhibiting an important pathophysiological role.

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“…Although human PNP is widely expressed in human tissues and is present in both the cytosol and the mitochondria, the highest activity is in peripheral red blood cells, blood granulocytes and lymphoid tissue [38]. Thymidine phosphorylase (TP) and uridine phosphorylase (UP) are also expressed at high levels in human blood and in tissues such as liver, intestine and brain [39].…”

Section: Nucleoside Phosphorylases a Biological Role A Target For Cmentioning

confidence: 99%

Nucleoside Phosphorylases

Lewkowicz

Iribarren

2006

COC

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Nucleoside phosphorylases (NPs) are transferases that catalyse the reversible cleavage of the glycosidic bond of ribo-or deoxyribo nucleosides, in the presence of inorganic phosphate, to generate the base and ribose-or deoxyribose-1-phosphate.Since pyrimidine as well as purine nucleoside phosphorylases exist, the combination of both enzymes makes possible the generation of purine nucleosides from pyrimidine ones. As a consequence, NPs from different sources, mainly bacterial, have been exploited as tools for the enzymatic synthesis of nucleoside analogues. These molecules are extensively used as antiviral and anticancer agents because of their ability to act as reverse transcriptase inhibitors or chain terminators in RNA or DNA synthesis.This review covers literature reports from 2000 on, focused mainly on the synthesis of nucleosides by free and immobilised microbial whole cells, along with some examples of modified nucleosides obtained by coupling transglycosylation to other enzymatic reactions.The biological aspects of NPs are also discussed since they became an interesting target for clinical applications due to their key role in nucleotide metabolism. Finally, brief comments about their structures and catalytic mechanisms are included.

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Plasma purine nucleoside phosphorylase in cancer patients

Cited by 24 publications

References 14 publications

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Evidence for purine nucleoside phosphorylase (PNP) release from rat C6 glioma cells

Nucleoside Phosphorylases

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