Differential Expression of Human Nucleoside Transporters in Normal and Tumor Tissue

Pennycooke, Micha; Chaudary, Naz; Shuralyova, Irina; Zhang, Ying; Coe, Imogen R.

doi:10.1006/bbrc.2000.4205

Cited by 169 publications

(157 citation statements)

References 19 publications

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“…NBTI partially inhibits ENTs at the nM concentration range ("es": equilibrative, NBTI sensitive type of ENTs, e.g., ENT1), whereas NBTI insensitive transporters are inhibited by NBTI only at the m M concentration range ("ei": equilibrative, NBTI insensitive type of ENTs, e.g., ENT2). The concentrative nucleoside transporter family (CNT transporters; unidirectional, sodium-dependent) includes six CNT transporter types (N1-N6) that are classi fi ed based on the types of nucleosides transported and sodium transport coupling Barnes et al 2006 ;Jennings et al 2001 ;Parkinson et al 2011 ;Pennycooke et al 2001 ;Ritzel et al 2001 ) .…”

Section: Transportersmentioning

confidence: 99%

“…Nucleoside levels, metabolic enzymes, transporters, and receptors are unevenly distributed in the human brain ; Barnes et al 2006 ;Dawson 1971 ;Fredholm et al 2001 ;Jennings et al 2001 ;Kovács et al 1998Kovács et al , 2010aNagata et al 1984 ;Norstrand et al 1984 ;Norstrand and Glantz 1980 ;Pennycooke et al 2001 ;Phillips and Newsholme 1979 ;Ritzel et al 2001 ) . In addition, nucleoside concentrations are dependent on age and gender (Kovács et al 2010b ) .…”

Section: Introductionmentioning

confidence: 99%

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Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

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Section: Transportersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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“…The unique monoclonal antibody 3E10 and its fragments are capable of penetrating living cells to deliver functional proteins to the cytosol and nuclei via ENT2, a cell-surface transporter that is highly expressed in human skeletal and cardiac muscle [18,19]. More impressively, its Fab fragment has been shown to be able to deliver a 305 kDa protein efficiently into cultured cells [16].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a recent study demonstrated that ERT with 3E10Fv-MTM1 fusion protein improved muscle function and pathology in mice with X-linked myotubular myopathy [17]. 3E10 penetrates cells via equilibrative nucleoside transporter 2 (ENT2) [18] that is expressed at high levels in human and rodent skeletal muscles and heart [19,20], making it an ideal vehicle for cytoplasmic delivery of therapeutic GAA in muscle tissues of Pompe disease. A 3E10-GAA fusion should enable ENT2-mediated uptake to clear extra-lysosomal glycogen in muscle fibers while retaining the ability to degrade lysosomal glycogen via M6PR-mediated uptake.…”

Section: Introductionmentioning

confidence: 99%

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease

Sun

Armstrong

et al. 2017

J Mol Med

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Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers Bcargo^proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95-and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95-and the 76 kDa forms but not the 150 kDa form.

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“…These results are in agreement with data obtained in previous studies on differences among neoplastic tissue and normal tissue or among neoplastic tissue and chronic inflammation, suggesting that laser microdissection is crucial to obtain more accurate data and address previously unanswerable questions arising from samples characterized by different cellular populations. 42,43 Indeed, as new cutting-edge quantitative expression analytical procedures and instruments are developed, more rigorous demands must also be placed on sample preparation Expression of drug-related genes in NSCLC techniques, including laser microdissection. The successive validated quantitative PCR analysis was a reliable, sensitive and specific technique to assess mRNA gene expression, even when sample material was limited, such as in lymph node metastasis.…”

Section: Expression Of Drug-related Genes In Nsclcmentioning

confidence: 99%

Expression of gemcitabine- and cisplatin-related genes in non-small-cell lung cancer

et al. 2009

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The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5 0 -nucleotidase (5 0 -NT), cytidine deaminase (CDA) and ribonucleotidereductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine-cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.

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Differential Expression of Human Nucleoside Transporters in Normal and Tumor Tissue

Cited by 169 publications

References 19 publications

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease

Expression of gemcitabine- and cisplatin-related genes in non-small-cell lung cancer

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