P2X7 receptor activity landscape in rat and human glioma cell lines

Abstract

P2X7 is a commonly expressed purinergic receptor, which functions as a cation-permeable channel in the plasma membrane. In certain circumstances, the receptor may also form a large transmembrane pore what results in cell death. P2X7 receptors control numerous physiological and pathological cellular processes and their overexpression is often associated with cancer progression. As nucleotides are important signaling molecules in the central nervous system, P2X7 plays also an important but ambiguous role in glioma biology with contrary observations originating from different glioma models. Therefore, the aim of our research was to investigate P2X7 receptor expression and functions in three human (U-87 MG, U-138 MG, U-251 MG) and one rat (C6) glioma cell lines. Although the receptor mRNA and protein were present in all the studied cells, we found profound differences in their level. We also encountered a problem with one human cell lines authenticity (U-87 MG) and excluded it from most of the experiments. Interestingly, there was no clear dependency between P2X7 receptor level, calcium signal and pore formation ability in the studied glioma lines. In U-138 human cell line, the receptor seemed to be inactive, while in U-251 human and C6 rat cell line its activation resulted in calcium influx and large pore formation. However, the viability of studied cells upon the administration of specific P2X7 agonist-BzATP-was not affected for U-138 and U-251, whereas for C6 cells a stimulatory effect was observed. Our results stress the variability of P2X7 signaling in glioma models and the need for future research which would take into account the complicated landscape of the receptor signaling in the brain.