| P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line. | |
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MedLine Citation:
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PMID: 22644907 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gliomas are the most lethal tumors of central nervous system. ATP is an important signaling molecule in CNS and it is a selective P2X7 purinergic receptor ligand at high concentrations. Herein, we investigated whether the activation of P2X7R might be implicated in death of a radiosensitive human glioma lineage. The effects of P2X7R agonists (ATP and BzATP) and irradiation (2 Gy) on glioma cells were analyzed by MTT assay and annexin-V/PI determination, whereas mRNA and protein P2X7R expression was assessed by qRT-PCR and flow cytometry, respectively. P2X7R pore formation was functionality examined by analyzing ethidium bromide uptake. The human glioma cells U-138 MG and U-251 MG were resistant to death when treated with either ATP (5 mM) or BzATP (100 μM), but the radiosensitive M059J glioma cells displayed a significant decrease of cell viability (32.4 ± 4.1 % and 25.6 ± 3.3 %, respectively). The M059J lineage expresses significantly higher mRNA P2X7R levels when compared to the U-138 MG and U-251 cell lines (0.40 ± 0.00; 0.28 ± 0.01, and 0.31 ± 0.01, respectively), and irradiation upregulated P2X7R expression (0.55 ± 0.08) in this lineage. Noteworthy, P2X7R protein doubled after irradiation on M059J lineage, and increased in 50 % and 42.6 % when comparing M059J-irradiated to irradiated U-138 MG and U-251 MG cells, respectively. Ethidium bromide uptake was significantly increased in 104 % and 77.8 % when comparing M059J to U-138 MG and U-251MG, respectively. Finally, the selective P2X7R antagonist A740003 significantly decreased the cell death caused by irradiation. We provide novel evidence indicating that M059J human glioma cell line is ATP-P2X7R sensitive, pointing out the relevance of the purinergic P2X7R on glioma radiosensitivity. |
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Authors:
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Marina Petersen Gehring; Talita Carneiro Brandão Pereira; Rafael Fernandes Zanin; Magali Carvalho Borges; Aroldo Braga Filho; Ana Maria Oliveira Battastini; Maurício Reis Bogo; Guido Lenz; Maria Martha Campos; Fernanda Bueno Morrone |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-05-28 |
Journal Detail:
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Title: Purinergic signalling Volume: 8 ISSN: 1573-9546 ISO Abbreviation: Purinergic Signal. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-10-22 Completed Date: 2013-03-20 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101250499 Medline TA: Purinergic Signal Country: Netherlands |
Other Details:
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Languages: eng Pagination: 729-39 Citation Subset: IM |
Affiliation:
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Laboratório de Farmacologia Aplicada, PUCRS, Av. Ipiranga, 6681, Prédio 12C, Sala 148, Partenon, Porto Alegre, RS, Brazil. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Cell Death / radiation effects Cell Line, Tumor Glioma / metabolism, radiotherapy* Humans Receptors, Purinergic P2X7 / metabolism* Up-Regulation / radiation effects |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Purinergic P2X7; 56-65-5/Adenosine Triphosphate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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