scholarly journals Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

2021 ◽  
Author(s):  
Maria Ellegaard ◽  
Tanja Hegner ◽  
Ming Ding ◽  
Lauriane Ulmann ◽  
Niklas Rye Jørgensen
Keyword(s):  
Knockout Mice ◽  
P2x7 Receptor ◽  
P2x4 Receptor ◽  
Bone Phenotype

The antihyperalgesic activity of a selective P2X7 receptor antagonist, A-839977, is lost in IL-1αβ knockout mice

2009 ◽  
Vol 204 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Prisca Honore ◽  
Diana Donnelly-Roberts ◽  
Marian Namovic ◽  
Chengmin Zhong ◽  
Carrie Wade ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Knockout Mice ◽  
P2x7 Receptor

scholarly journals Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

2018 ◽  
Vol 14 (4) ◽  
pp. 459-469 ◽  
Author(s):  
Anna S. Miteva ◽  
Alexander E. Gaydukov ◽  
Valery I. Shestopalov ◽  
Olga P. Balezina
Keyword(s):  
Knockout Mice ◽  
P2x7 Receptor ◽  
Neuromuscular Transmission ◽  
Pannexin 1

scholarly journals P2X7 Receptor Indirectly Regulates the JAM-A Protein Content via Modulation of GSK-3β

2019 ◽  
Vol 20 (9) ◽  
pp. 2298 ◽  
Author(s):  
Karl-Philipp Wesslau ◽  
Anabel Stein ◽  
Michael Kasper ◽  
Kathrin Barth
Keyword(s):  
Epithelial Cells ◽  
Knockout Mice ◽  
Protein Level ◽  
P2x7 Receptor ◽  
Alveolar Epithelial Cells ◽  
Strong Increase ◽  
Alveolar Epithelial ◽  
Gsk 3Β ◽  
Precision Cut Lung Slices

The alveolar epithelial cells represent an important part of the alveolar barrier, which is maintained by tight junction proteins, particularly JAM-A, occludin, and claudin-18, which regulate paracellular permeability. In this study, we report on a strong increase in epithelial JAM-A expression in P2X7 receptor knockout mice when compared to the wildtype. Precision-cut lung slices of wildtype and knockout lungs and immortal epithelial lung E10 cells were treated with bleomycin, the P2X7 receptor inhibitor oxATP, and the agonist BzATP, respectively, to evaluate early changes in JAM-A expression. Biochemical and immunohistochemical data showed evidence for P2X7 receptor-dependent JAM-A expression in vitro. Inhibition of the P2X7 receptor using oxATP increased JAM-A, whereas activation of the receptor decreased the JAM-A protein level. In order to examine the role of GSK-3β in the expression of JAM-A in alveolar epithelial cells, we used lithium chloride for GSK-3β inhibiting experiments, which showed a modulating effect on bleomycin-induced alterations in JAM-A levels. Our data suggest that an increased constitutive JAM-A protein level in P2X7 receptor knockout mice may have a protective effect against bleomycin-induced lung injury. Bleomycin-treated precision-cut lung slices from P2X7 receptor knockout mice responded with a lower increase in mRNA expression of JAM-A than bleomycin-treated precision-cut lung slices from wildtype mice.

Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages

2012 ◽  
Vol 419 (2) ◽  
pp. 374-380 ◽  
Author(s):  
Ayumi Kawano ◽  
Mitsutoshi Tsukimoto ◽  
Taisei Noguchi ◽  
Noriyuki Hotta ◽  
Hitoshi Harada ◽  
...  
Keyword(s):  
Cell Death ◽  
P2x7 Receptor ◽  
P2x4 Receptor ◽  
Mouse Macrophages ◽  
Dependent Cell

Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test

Neuroscience ◽  
2011 ◽  
Vol 189 ◽  
pp. 170-177 ◽  
Author(s):  
A.A. Boucher ◽  
J.C. Arnold ◽  
G.E. Hunt ◽  
A. Spiro ◽  
J. Spencer ◽  
...  
Keyword(s):  
Knockout Mice ◽  
P2x7 Receptor ◽  
Forced Swim Test ◽  
Swim Test ◽  
Forced Swim ◽  
Fos Expression

P2X7 receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in the piriform cortex

2020 ◽  
Vol 714 ◽  
pp. 134575
Author(s):  
Kristie Leigh Smith ◽  
Stephanie M. Todd ◽  
Aurelie Boucher ◽  
Maxwell R. Bennett ◽  
Jonathon C. Arnold
Keyword(s):  
Knockout Mice ◽  
P2x7 Receptor ◽  
Piriform Cortex ◽  
Brain Activation ◽  
Biting Behaviour

scholarly journals Basal bone phenotype and increased anabolic responses to intermittent parathyroid hormone in healthy male COX-2 knockout mice

Bone ◽  
2010 ◽  
Vol 47 (2) ◽  
pp. 341-352 ◽  
Author(s):  
Manshan Xu ◽  
Shilpa Choudhary ◽  
Olga Voznesensky ◽  
Qi Gao ◽  
Douglas Adams ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Knockout Mice ◽  
Healthy Male ◽  
Bone Phenotype ◽  
Basal Bone ◽  
Cox 2

P2X4 receptor regulates P2X7 receptor-dependent IL-1β and IL-18 release in mouse bone marrow-derived dendritic cells

2013 ◽  
Vol 432 (3) ◽  
pp. 406-411 ◽  
Author(s):  
Hayato Sakaki ◽  
Takuya Fujiwaki ◽  
Mitsutoshi Tsukimoto ◽  
Ayumi Kawano ◽  
Hitoshi Harada ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
P2x7 Receptor ◽  
Mouse Bone Marrow ◽  
P2x4 Receptor

scholarly journals Novel Evidence That Extracellular Adenosine Triphosphate (ATP), As a Purinergic Signaling Mediator, Activates Mobilization By Engaging a P2X4 Ligand-Gated Cation Channel Receptor Expressed on the Surface of Hematopoietic and Innate Immunity Cells

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4472-4472 ◽  
Author(s):  
Kamila Bujko ◽  
Mateusz Adamiak ◽  
Arjun Thapa ◽  
Magdalena Kucia ◽  
Janina Ratajczak ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Adenosine Triphosphate ◽  
Small Molecule ◽  
Nlrp3 Inflammasome ◽  
P2x7 Receptor ◽  
Purinergic Signaling ◽  
Hematopoietic Cells ◽  
Wild Type ◽  
P2x4 Receptor ◽  
Molecule Inhibitor

Background . Adenosine triphosphate (ATP) is an important nucleotide involved in intracellular energy transfer, but it is also released from activated cells into the extracellular space as a crucial component of the purinergic signaling network. Purinergic signaling is an ancient form of extracellular signaling that is mediated by ATP and other extracellular nucleotides (EXNs). Purinergic receptors for EXNs are expressed on the surface of all cells in the body; are represented by several families of P1, P2X, and P2Y receptors; and are among the most abundant receptors in living organisms. Of all these receptors, the P2X receptor family is most highly specific for ATP signaling and consists of seven members (P2X1-7). We recently reported that by activating the P2X7 receptor ATP activates the Nlrp3 inflammasome in hematopoietic cells and significantly enhances G-CSF-induced mobilization of hematopoietic stem progenitor cells (HSPCs, Leukemia 2018, 32:1920-1931). Hypothesis. Since P2X7-KO mice still mobilize some HSPCs, we hypothesized that, in addition to the P2X7 receptor, other receptors from this family also play a role in the mobilization process.Materials and Methods. RT-PCR and FACS were employed to phenotype human and murine bone marrow (BM) mononuclear cells (MNCs) as well as sorted HSCs for expression of P2X receptors. Mobilization studies were performed in wild type mice in which the P2X4 receptor was blocked by the specific small-molecule inhibitor PSB12054 and in P2X7-KO animals. Following mobilization, we measured i) the total number of white blood cells (WBCs) and ii) the number of circulating clonogenic colony-forming unit granulocyte/macrophage (CFU-GM) progenitors and Sca-1+c-kit+lineage- (SKL) cells circulating in PB. We also evaluated activation of the Nlrp3 inflammasome as well as other inflammasomes expressed in hematopoietic cells, including Aim2, Nlrp1a, Nlrp1b, and Nlrc4. Results. We found that, of all the receptors of the P2X family, two members, P2X7 and P2X4, are highly expressed on the surface of murine and human MNCs and HSPCs (Figure 1a). Activation of both receptors on the surface of innate immunity CD11b+Gr-1+ cells resulted in activation of the Nlrp3, Nlrp1a, Nlrp1b, and Aim2 inflammasomes. Inhibition of the P2X4 receptor by a specific small-molecule inhibitor decreased G-CSF- and AMD3100-induced mobilization in wild type mice (Figure 1b). Interestingly, we observed differences during AMD3100 mobilization, namely that while P2X7-KO deficiency resulted in decreased G-CSF-induced mobilization and did not affect AMD3100 mobilization efficiency, P2X4 inhibition, by contrast, led to a profound decrease in both G-CSF- and AMD3100-induced mobilization efficiency. Conclusions. Our results further support an important role for purinergic signaling in the mobilization of HSPCs. We also demonstrated that P2X7 and P2X4 receptors, which are highly expressed on human and murine hematopoietic cells, are involved in G-CSF-induced mobilization by activating the Nlrp3, Nlrp1a, Nlrp1b and Aim2 inflammasomes. By contrast, AMD3100-induced mobilization requires expression of P2X4 but not P2X7 receptors, which implies the involvement of different mechanisms and indicates that P2X7 deficiency can be compensated by the P2X4 receptor. Currently, we are performing RNASeq studies to identify differences in the G-CSF- and AMD3100-induced pathways in the mobilization process. These investigations will shed more light on the molecular pathways involved in the egress of HSPCs from BM into PB and will help to design better mobilization protocols in cases of poor mobilizers. Figure 1 Disclosures No relevant conflicts of interest to declare.

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