Topic Editors

Department of Medicine, Université de Montréal, and Centre de recherche, Centre hospitalier de l'Université de Montréal, (CRCHUM), Montréal, QC, Canada
Dr. Francis Boudreault
Department of Medicine, Université de Montréal, and Centre de recherche, Centre hospitalier de l'Université de Montréal, (CRCHUM), Montréal, QC, Canada

ATP Release in Health and Disease

Abstract submission deadline
closed (29 August 2021)
Manuscript submission deadline
closed (29 October 2021)
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Topic Information

Dear Colleagues,

The release of cellular adenosine triphosphate (ATP), along with other nucleotides, triggers the purinergic signaling system that is expressed in virtually all types of cells and tissues. By autocrine/paracrine stimulation of purinergic receptors, released extracellular nucleotides regulate numerous physiological processes, including neurotransmission, mucocilliary clearance in the lungs, thrombocyte aggregation, neutrophils migration, local blood flow, and bone remodeling. ATP release is also associated with the pathogenesis of a number of diseases and clinical complications, including cancer, acute respiratory distress syndrome, and ventilator-induced lung injury. There is increasing interest in the therapeutic potential of purinergic compounds in a wide range of disease conditions.

Despite significant advances in the molecular, functional, and pharmacological characterization of numerous purinoreceptors as well as ectoenzymes involved in the metabolism and conversion of extracellular nucleotides, the initiating step of the purinergic signaling—the release of ATP—remains least understood. Multiple release pathways/mechanisms have been proposed, including the exocytosis of ATP-loaded vesicles, as well as a variety of conductive pathways, including bacterial toxins. Even though much progress has been made, in many cases there is still an active debate about the precise nature of the specific conductive pathways of the release, their molecular identity, biophysical characteristics, and physiological regulation. Recently, there is also more appreciation of ATP release resulting from cell membrane injury and cell lysis as important contributors to normal cell signaling.

This Special Issue intends to present the latest developments in the field, covering multiple areas of ATP release research and different points of view regarding the underlying mechanisms. We will welcome original research, reviews, and short reports on various aspects of ATP release as well as technical reports on novel or improved experimental approaches or imaging tools for studying cellular ATP release.

Prof. Dr. Ryszard Grygorczyk
Dr. Francis Boudreault
Topic Editors

Article processing charge will be waived for all accepted manuscripts in Physiologia from 1 May to 31 December 2021.

Keywords

  • ATP secretion
  • purinergic signaling
  • mechano-sensation
  • luciferase

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Life
life
3.2 4.3 2011 18 Days CHF 2600
Physiologia
physiologia
- - 2021 27.9 Days CHF 1000

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Published Papers (5 papers)

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12 pages, 2368 KiB  
Article
Sphingosine-1-Phosphate Induces ATP Release via Volume-Regulated Anion Channels in Breast Cell Lines
by Kishio Furuya, Hiroaki Hirata, Takeshi Kobayashi and Masahiro Sokabe
Life 2021, 11(8), 851; https://doi.org/10.3390/life11080851 - 19 Aug 2021
Cited by 4 | Viewed by 3217
Abstract
High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated [...] Read more.
High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated anion channels (VRACs) in breast cell lines using an ATP luminescence imaging system. We detected a slowly rising diffuse pattern of ATP release that was only observed in undifferentiated cells, not in differentiated primary cultured cells. This was confirmed by suppression with DCPIB, a blocker of VRACs, and shRNA for LRRC8A, an indispensable subunit of VRACs. We herein demonstrated that the inflammatory mediator sphingosine-1-phosphate (S1P), which exists abundantly in the cancer microenvironment, induced a diffuse pattern of ATP release isovolumetrically. The response was dose-dependent and suppressed by the knock-down of LRRC8A. It was also suppressed by blockers of S1P receptor 1 and 2 (W146 and JTE013, respectively). RTqPCR demonstrated the prominent presence of S1PR1 and S1PR2 mRNAs. We discussed the roles of S1P-induced ATP release in the cancer microenvironment. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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21 pages, 6793 KiB  
Review
Lytic Release of Cellular ATP: Physiological Relevance and Therapeutic Applications
by Ryszard Grygorczyk, Francis Boudreault, Olga Ponomarchuk, Ju Jing Tan, Kishio Furuya, Joseph Goldgewicht, Falonne Démèze Kenfack and François Yu
Life 2021, 11(7), 700; https://doi.org/10.3390/life11070700 - 16 Jul 2021
Cited by 15 | Viewed by 3265
Abstract
The lytic release of ATP due to cell and tissue injury constitutes an important source of extracellular nucleotides and may have physiological and pathophysiological roles by triggering purinergic signalling pathways. In the lungs, extracellular ATP can have protective effects by stimulating surfactant and [...] Read more.
The lytic release of ATP due to cell and tissue injury constitutes an important source of extracellular nucleotides and may have physiological and pathophysiological roles by triggering purinergic signalling pathways. In the lungs, extracellular ATP can have protective effects by stimulating surfactant and mucus secretion. However, excessive extracellular ATP levels, such as observed in ventilator-induced lung injury, act as a danger-associated signal that activates NLRP3 inflammasome contributing to lung damage. Here, we discuss examples of lytic release that we have identified in our studies using real-time luciferin-luciferase luminescence imaging of extracellular ATP. In alveolar A549 cells, hypotonic shock-induced ATP release shows rapid lytic and slow-rising non-lytic components. Lytic release originates from the lysis of single fragile cells that could be seen as distinct spikes of ATP-dependent luminescence, but under physiological conditions, its contribution is minimal <1% of total release. By contrast, ATP release from red blood cells results primarily from hemolysis, a physiological mechanism contributing to the regulation of local blood flow in response to tissue hypoxia, mechanical stimulation and temperature changes. Lytic release of cellular ATP may have therapeutic applications, as exemplified by the use of ultrasound and microbubble-stimulated release for enhancing cancer immunotherapy in vivo. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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14 pages, 1756 KiB  
Article
Mechanosensitive TRPV4 Channel-Induced Extracellular ATP Accumulation at the Acupoint Mediates Acupuncture Analgesia of Ankle Arthritis in Rats
by Yawen Zheng, Weimin Zuo, Dan Shen, Kaiyu Cui, Meng Huang, Di Zhang, Xueyong Shen and Lina Wang
Life 2021, 11(6), 513; https://doi.org/10.3390/life11060513 - 31 May 2021
Cited by 13 | Viewed by 2656
Abstract
(1) Background: Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular [...] Read more.
(1) Background: Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular ATP (eATP) mobilization preceded adenosine accumulation, which involved local activation of mechanosensitive channels, especially TRPV4 protein. (2) Methods: AP was applied at the injured-side Zusanli acupoint (ST36) of acute ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in microdialysate from the acupoints was determined by luminescence assay. (3) Results: AP analgesic effect was significantly suppressed by pre-injection of GdCl3 or ruthenium red in ST36, the wide-spectrum inhibitors of mechanosensitive channels, or by HC067047, a specific antagonist of TRPV4 channels. Microdialysate determination revealed a needling-induced transient eATP accumulation that was significantly decreased by pre-injection of HC067047. Additionally, preventing eATP hydrolysis by pre-injection of ARL67156, a non-specific inhibitor of ecto-ATPases, led to the increase in eATP levels and the abolishment of AP analgesic effect. (4) Conclusions: These observations indicate that needling-induced transient accumulation of eATP, due to the activation of mechanosensitive TRPV4 channels and the activities of ecto-ATPases, is involved in the trigger mechanism of AP analgesia. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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19 pages, 2491 KiB  
Review
The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications
by Ravshan Z. Sabirov, Md. Rafiqul Islam, Toshiaki Okada, Petr G. Merzlyak, Ranokhon S. Kurbannazarova, Nargiza A. Tsiferova and Yasunobu Okada
Life 2021, 11(6), 509; https://doi.org/10.3390/life11060509 - 31 May 2021
Cited by 15 | Viewed by 3542
Abstract
The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans [...] Read more.
The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to-voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Maxi-Cl channel. Its identification as a complex with SLCO2A1 as a core pore-forming component and two auxiliary regulatory proteins, annexin A2 and S100A10 (p11), explains the activation mechanism as Tyr23 dephosphorylation at ANXA2 in parallel with calcium binding at S100A10. In the resting state, SLCO2A1 functions as a prostaglandin transporter whereas upon activation it turns to an anion channel. As an efficient pathway for chloride, Maxi-Cl is implicated in a number of physiologically and pathophysiologically important processes, such as cell volume regulation, fluid secretion, apoptosis, and charge transfer. Maxi-Cl is permeable for ATP and other small signaling molecules serving as an electrogenic pathway in cell-to-cell signal transduction. Mutations at the SLCO2A1 gene cause inherited bone and gut pathologies and malignancies, signifying the Maxi-Cl channel as a perspective pharmacological target. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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10 pages, 692 KiB  
Review
Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance
by Catharina van Heusden, Barbara R. Grubb, Brian Button and Eduardo R. Lazarowski
Life 2021, 11(5), 430; https://doi.org/10.3390/life11050430 - 11 May 2021
Cited by 9 | Viewed by 2804
Abstract
Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated [...] Read more.
Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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