Abstract
P2X7 is an ionotropic nucleotide receptor, forming the cation channel upon ATP stimulation. It can also function as a large membrane pore as well as transmit ATP-dependent signal without forming a channel at all. P2X7 activity in somatic cells is well-known, but remains poorly studied in glioma tumors. The current paper presents the comprehensive study of P2X7 activity in C6 and glioma cell line showing the wide range of effects the receptor has on glioma biology. We observed that P2X7 stimulation boosts glioma cell proliferation and increases cell viability. P2X7 activation promoted cell adhesion, mitochondria depolarization, and reactive oxygen species overproduction in C6 cells. P2X7 receptor also influenced glioma tumor growth in vivo via activation of pro-survival signaling pathways and ATP release. Treatment with Brilliant Blue G, a selective P2X7 antagonist, effectively inhibited glioma tumor development; decreased the expression of negative prognostic cancer markers pro-survival and epithelial-mesenchymal transition (EMT)-related proteins; and modulated the immune response toward glioma tumor in vivo. Finally, pathway-specific enrichment analysis of the microarray data from human patients also showed an upregulation of P2X7 receptor in gliomas from grades I to III. The presented results shed more light on the role of P2X7 receptor in the biology of this disease.
Highlights
P2X7 purinoceptor belongs to the subfamily of ligand (ATP)-gated ionotropic P2X receptors and is a trimeric ion channel that modulates transmembrane calcium, sodium, and potassium ion movement [1]
The level of p38 MAPK and Akt phosphorylation was higher after P2X7 activation, to the total protein level of chaperones HSPA1 and HSPA5, and glioma stem cell marker CD133
Activated P2X7 receptor led to mitochondria depolarization and increased ROS production in glioma C6 cells
Summary
P2X7 purinoceptor belongs to the subfamily of ligand (ATP)-gated ionotropic P2X receptors and is a trimeric ion channel that modulates transmembrane calcium, sodium, and potassium ion movement [1]. The best characterized activity of P2X7 is its role in ATP-induced IL-1β release from macrophages and microglia [3]. Extracellular ATP induces P2X7 activation and channel opening for Ca2+ and Na+ influx and K + efflux [4, 5]. Sustained stimulation of P2X7 with higher ATP doses or repeated stimulation with sequential ATP pulses induces the formation of a large pore permeable for molecules up to 900 Da [6, 7]. This ability is associated with an intact, non-mutated C-terminal domain of the receptor [8]. The ATP-induced pore formation leads to cell death [9] in various types of cells: macrophages [10, 11], microglial cells [12], neurons [13], and some cancer cells [14, 15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
