Document Detail

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line.
MedLine Citation:
PMID:  22644907     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-28
Journal Detail:
Title:  Purinergic signalling     Volume:  8     ISSN:  1573-9546     ISO Abbreviation:  Purinergic Signal.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-03-20     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  101250499     Medline TA:  Purinergic Signal     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  729-39     Citation Subset:  IM    
Laboratório de Farmacologia Aplicada, PUCRS, Av. Ipiranga, 6681, Prédio 12C, Sala 148, Partenon, Porto Alegre, RS, Brazil.
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MeSH Terms
Adenosine Triphosphate / metabolism
Cell Death / radiation effects
Cell Line, Tumor
Glioma / metabolism,  radiotherapy*
Receptors, Purinergic P2X7 / metabolism*
Up-Regulation / radiation effects
Reg. No./Substance:
0/Receptors, Purinergic P2X7; 56-65-5/Adenosine Triphosphate

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