Purinoceptors on Neuroglia

Verkhrasky, Alexei; Krishtal, O. A.; Burnstock, Geoffrey

doi:10.1007/s12035-009-8063-2

Cited by 199 publications

(99 citation statements)

References 255 publications

(255 reference statements)

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“…4), and after irradiation (2 Gy), the radioresistant lineages (U-138 MG and U-251 MG) did not have their P2X7R protein levels increased, as expected after an injury [24]. Moreover, the P2X7R is unique in its ability to produce a large transmembrane pore upon intense stimulation [5]. Herein, we have shown that P2X7R pore is significantly more functional on M059J cell line when compared to U-138 MG and U-251 MG (Fig.…”

Section: Discussionmentioning

confidence: 63%

“…5a, the M059J cells (black line) showed a significant higher capacity of ethidium bromide uptake, when compared to U-138 MG (gray line) and U-251 MG (dotted line) (MFI 4763.5± 198.5, 1364.0±102, and 3001.5±42. 5), what is probably related to its ATP-P2X7R sensitivity.…”

Section: Ethidium Bromide Uptakementioning

confidence: 97%

“…When this receptor is activated by ATP binding, it opens a pore through which molecules up to 900 Da can pass. However, this pore opening requires prolonged exposure to ATP, and the full activation is reached only at millimolar ATP concentrations [2,5]. Some studies have reported that P2X7 is responsible for ATP-induced cell death in various cell types through mechanisms involving necrotic features, such as swelling, loss of membrane integrity and also apoptotic features, such as shrinking and phosphatidylserine externalization [2,6,7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line

Gehring

Pereira

Zanin

et al. 2012

Purinergic Signalling

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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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Section: Discussionmentioning

confidence: 63%

Section: Ethidium Bromide Uptakementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line

Gehring

Pereira

Zanin

et al. 2012

Purinergic Signalling

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“…Adenosine 5Ј-triphosphate (ATP) is a highly important biomolecule in living cells: It plays a central role in cell energy metabolism and also serves directly or indirectly in a number of cell signaling processes (1)(2)(3). The intracellular concentration of ATP is believed to oscillate in some eukaryotic cells, e.g.…”

mentioning

confidence: 99%

“…Oscillations only occur when the cell density is beyond a certain critical value (15,(17)(18)(19). The oscillations in glycolysis are usually monitored as oscillations in the autofluorescence of NADH, but also time-resolved oscillations in CO 2 evolution (20), mitochondrial membrane potential (21,22), and intracellular pH (pH i ) 2 (16) have been recorded. The oscillations in mitochondrial membrane potential and in intracellular pH were suggested to be caused by oscillating activities of the F 0 F 1 ATPase and the plasma membrane ATPase (PMA1) caused by oscillations in intracellular ATP (16).…”

mentioning

confidence: 99%

Time-resolved Measurements of Intracellular ATP in the Yeast Saccharomyces cerevisiae using a New Type of Nanobiosensor

Özalp

Pedersen

Nielsen

et al. 2010

Journal of Biological Chemistry

106

109

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Adenosine 5-triphosphate is a universal molecule in all living cells, where it functions in bioenergetics and cell signaling. To understand how the concentration of ATP is regulated by cell metabolism and in turn how it regulates the activities of enzymes in the cell it would be beneficial if we could measure ATP concentration in the intact cell in real time. Using a novel aptamer-based ATP nanosensor, which can readily monitor intracellular ATP in eukaryotic cells with a time resolution of seconds, we have performed the first on-line measurements of the intracellular concentration of ATP in the yeast Saccharomyces cerevisiae. These ATP measurements show that the ATP concentration in the yeast cell is not stationary. In addition to an oscillating ATP concentration, we also observe that the concentration is high in the starved cells and starts to decrease when glycolysis is induced. The decrease in ATP concentration is shown to be caused by the activity of membrane-bound ATPases such as the mitochondrial F 0 F 1 ATPase-hydrolyzing ATP and the plasma membrane ATPase (PMA1). The activity of these two ATPases are under strict control by the glucose concentration in the cell. Finally, the measurements of intracellular ATP suggest that 2-deoxyglucose (2-DG) may have more complex function than just a catabolic block. Surprisingly, addition of 2-DG induces only a moderate decline in ATP. Furthermore, our results suggest that 2-DG may inhibit the activation of PMA1 after addition of glucose.Adenosine 5Ј-triphosphate (ATP) is a highly important biomolecule in living cells: It plays a central role in cell energy metabolism and also serves directly or indirectly in a number of cell signaling processes (1-3). The intracellular concentration of ATP is believed to oscillate in some eukaryotic cells, e.g. in ␤-cells (4) and in cells of the yeast Saccharomyces cerevisiae (5). However, changes in cytoplasmic ATP concentration with high time resolution have so far only been measured in a few circumstances (6, 7), mainly because methods for such continuous measurements are not generally available, or, in the case of NMR, require very high densities of cells or tissue (8).The lack of time-resolved measurements has prohibited the understanding of how the level of ATP and other intracellular metabolites are regulated in the cell and how ATP in turn regulates a number of cellular processes. Most current measurements of ATP in cells use extraction of the cell content and measure the concentration of ATP in the extract by various off-line methods such as HPLC (9), luciferase (10), or other enzyme-based methods (11). A few protein-based sensors exist (6,7,(12)(13)(14), which in principle allow for time-resolved measurements of intracellular ATP or ADP, but some of these methods entail expression of the sensor molecule in situ, which is not always possible. Hence, although it is expected that the intracellular concentration of ATP is anything but stationary, this has not been verified by real-time measurements, except in a few cases where ...

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Astroglia

2013

Glial Physiology and Pathophysiology

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Purinoceptors on Neuroglia

Cited by 199 publications

References 255 publications

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line

Time-resolved Measurements of Intracellular ATP in the Yeast Saccharomyces cerevisiae using a New Type of Nanobiosensor

Astroglia

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