Large pore formation uniquely associated with P2X7 purinergic receptor channels. Focus on “Are second messengers crucial for opening the pore associated with P2X7 receptor?”

2005 ◽  
Vol 288 (2) ◽  
pp. C240-C242 ◽  
Author(s):  
Lihua Liang ◽  
Erik M. Schwiebert
Keyword(s):  
P2x7 Receptor ◽  
Pore Formation ◽  
Purinergic Receptor ◽  
Second Messengers ◽  
Large Pore

scholarly journals P2X7 receptor activity landscape in rat and human glioma cell lines

2020 ◽  
Author(s):  
Damian Matyśniak ◽  
Natalia Nowak ◽  
Vira Chumak ◽  
Paweł Pomorski
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
P2x7 Receptor ◽  
Pore Formation ◽  
Glioma Cell ◽  
Purinergic Receptor ◽  
Receptor Expression ◽  
Calcium Signal ◽  
Glioma Cell Lines

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.

scholarly journals Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin

1997 ◽  
Vol 185 (3) ◽  
pp. 579-582 ◽  
Author(s):  
Davide Ferrari ◽  
Paola Chiozzi ◽  
Simonetta Falzoni ◽  
Stefania Hanau ◽  
Francesco Di  Virgilio
Keyword(s):  
Plasma Membrane ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Present Report ◽  
Physiological Role ◽  
Bacterial Endotoxin ◽  
Microglial Cells

Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.

scholarly journals Purinergic P2X7 Receptor: A Cation Channel Sensitive to Tumor Microenvironment

2019 ◽  
Vol 14 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Giorgia Scarpellino ◽  
Tullio Genova ◽  
Luca Munaron
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Purinergic Signalling ◽  
Cancer Therapies ◽  
Cell Functions ◽  
Anti Cancer ◽  
Purinergic P2x7 Receptor ◽  
And Function

Background: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 Receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial.Objective:Current review was conducted to check involvement of P2X7R use in cancer treatment.Methods:We review the most recent patents focused on the use of P2X7R in the treatment of cancer.Results:P2X7R is an intriguing purinergic receptor that plays different roles in tumor progression.Conclusion:Powerful strategies able to selectively interfere with its expression and function should reveal helpful in the development of new anti-cancer therapies.

scholarly journals Epidermal Growth Factor Facilitates Epinephrine Inhibition of P2X7-Receptor-Mediated Pore Formation and Apoptosis: A Novel Signaling Network

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 164-174 ◽  
Author(s):  
Liqin Wang ◽  
Ying-Hong Feng ◽  
George I. Gorodeski
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
P2x7 Receptor ◽  
Pore Formation ◽  
Cell Number ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

Epidermal growth factor (EGF), epinephrine, and the P2X7 receptor system regulate growth of human uterine cervical epithelial cells, but little is known about how these systems intercommunicate in exerting their actions. The objective of this study was to understand the mechanisms of EGF and epinephrine regulation of growth of cervical cells. Treatment of cultured CaSki cells with 0.2 nm EGF increased cell number via a PD98059-sensitive pathway. Treatment with 2 nm epinephrine increased cell number, and the effect was facilitated by cotreatment with EGF. Whereas the effect of EGF alone involved up-regulation of [3H]-thymidine incorporation and an increase in cell proliferation, the effect of epinephrine was mediated by inhibition of apoptosis. Epinephrine inhibited apoptosis induced by the P2X7 receptor ligand 2′,3′-0-(4-benzoylbenzoyl)-ATP, by attenuation of P2X7 receptor plasma membrane pore formation. Cotreatment with EGF facilitated epinephrine effect via a phosphoinositide 3-kinase-dependent mechanism. CaSki cells express the β2-adrenoceptor, and the epinephrine antiapoptotic effect could be mimicked by β2-adrenoceptor agonists and by activators of adenylyl cyclase. Likewise, the effect could be blocked by β2-adrenoceptor blockers and by the inhibitor of protein kinase-A H-89. Western immunoblot analysis revealed that epinephrine decreased the levels of the glycosylated 85-kDa form of the P2X7 receptor and increased receptor degradation, and that EGF potentiated these effects of epinephrine. EGF did not affect cellular levels of the β2-adrenoceptor. In contrast, EGF, acting via the EGF receptor, augmented β2-adrenoceptor recycling, and it inhibited β2-adrenoceptor internalization via a phosphoinositide 3-kinase-dependent mechanism. We conclude that, in cervical epithelial cells, EGF has a dual role: as mitogen, acting via the MAPK/MAPK kinase pathway, and as an antiapoptotic factor by facilitating epinephrine effect and resulting in greater expression of β2-adrenoceptors in the plasma membrane. These findings underscore a novel signaling network of communication between the receptor tyrosine kinases, the G protein-coupled receptors, and the purinergic P2X7 receptor.

scholarly journals Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150496 ◽  
Author(s):  
Shuji Matsuoka ◽  
Yasuyuki Ishii ◽  
Atsuhito Nakao ◽  
Masaaki Abe ◽  
Naomi Ohtsuji ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
Pore Formation ◽  
Class Ii ◽  
Hla Class Ii ◽  
Lymphoma Cell ◽  
Large Pore
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