Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody

Kaczmarek-Hájek, Karina; Zhang, Jiong; Kopp, R.; Grosche, Antje; Rissiek, Björn; Saul, Annika; Bruzzone, Santina; Engel, Tobías; Jooss, Tina; Krautloher, Anna; Schuster, Stefanie; Magnus, Tim; Stadelmann, Christine; Sirko, Swetlana; Koch-Nolte, Friedrich; Eulenburg, Volker; Nicke, Annette

doi:10.7554/elife.36217

Cited by 151 publications

(213 citation statements)

References 64 publications

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“…et al, 2017). The P2X7R is widely expressed in diverse tissues, including hematopoietic cells (Feng et al, 2016), neurons (Miras-Portugal et al, 2017), glia (Stokes et al, 2015;Kaczmarek-Hajek et al, 2018), bone (Agrawal and Gartland, 2015), muscle (Fabbrizio et al, 2019), endothelium (Green et al, 2018), epithelium (Woods et al, 2012), and immune cells (Ferrari et al, 1997). In the exocrine pancreas, P2X7Rs have been shown to be primarily expressed in pancreatic ductal cells where they may contribute to secretory regulation through induction of cation fluxes and interaction with cholinergic signaling (Novak et al, 2010;Burnstock and Novak, 2012).…”

Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren's syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

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Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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“…P2X7 is also expressed in central nervous system cells: microglia, astrocytes and oligodendrocytes, whereas its presence in neurons is still a subject of the debate (Illes et al, 2017;Miras-Portugal et al, 2017;Kaczmarek-Hajek et al, 2018). Importantly, glia and neurons use the extracellular ATP to communicate and to maintain the homeostasis in the brain; moreover, ATP may be also released from damaged CNS cells (Rivera et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor activity landscape in rat and human glioma cell lines

2020

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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.

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“…In the presence of extracellular ATP, P2X 7 receptors open so as to allow the passage of cations into cells, leading to a change in membrane potential. Such as scenario is common in many neural subtypes within the retina, as well as other cell types in the enteric and central nervous system . In contrast, in the absence of ATP, the extracellular part of the P2X 7 receptor can bind to the surface of dead and dying cells to mediate phagocytosis …”

Section: The Role Of Scavenger Receptors In the Development Of Early Amdmentioning

confidence: 99%

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Fletcher

2020

Ophthalmic Physiologic Optic

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Purpose Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in industrialised nations. Based on genetics, as well as proteome analysis of drusen, the role the innate immune system in the development and/or progression of the disease is well established. Mononuclear phagocytes, such as microglia and monocytes, play critical roles in innate immunity. Here, the role of retinal microglia in mediating normal retinal function, and how these cells change with age is discussed, so as to understand their role in the development and progression of AMD. Recent findings It is now known that microglia dynamically survey the neural environment, responding rapidly to even the most subtle neural injury. The dynamic and phagocytic roles of microglia can change with age contributing to alteration in the response of these cells to damage with age. Accumulation of innate immune cells in the subretinal space is a hallmark feature of the development of AMD, reflecting either an increase in migration of monocytes into the retina, or a failure of immune cell elimination from the retina. Furthermore, changes in phagocytic ability of immune cells could contribute to the accumulation of drusen deposits in the posterior eye. Summary An overview of how retinal microglia maintain retinal homeostasis under normal conditions is provided, and then how they contribute to each stage of AMD. In addition, circulating monocytes are altered in those with AMD, contributing to the overall inflammatory state. Understanding the role of cells of the innate immune system in AMD may uncover novel therapeutic targets with which to reduce either the development or progression of disease.

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Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody

Cited by 151 publications

References 64 publications

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2X7 receptor activity landscape in rat and human glioma cell lines

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

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