Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human DOI Creative Commons
Manju Tewari,

Stephanie Michalski,

Terrance M. Egan

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 161 - 161

Published: Jan. 16, 2024

P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in variety cells. Five the members sensitive to low concentrations extracellular ATP, while P2X6 receptor has an unknown affinity. The last subtype, P2X7 receptor, is unique requiring millimolar fully activate humans. This sensitivity imparts agonist with ability act as damage-associated molecular pattern triggers innate immune response elevated levels ATP accompany inflammation tissue damage. In this review, we focus on microglia because they primary cells central nervous system, or its synthetic analog, BzATP. We start by introducing purinergic then briefly consider roles play neurodevelopment disease referencing both original works relevant reviews. Next, move role initiating and/or modulating immunity system. While most data review involve work mice rats, highlight human studies P2X7R whenever possible.

Language: Английский

Extracellular ATP: A Feasible Target for Cancer Therapy DOI Creative Commons
Valentina Vultaggio-Poma, Alba Clara Sarti, Francesco Di Virgilio

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(11), P. 2496 - 2496

Published: Nov. 17, 2020

Adenosine triphosphate (ATP) is one of the main biochemical components tumor microenvironment (TME), where it can promote progression or suppression depending on its concentration and specific ecto-nucleotidases receptors expressed by immune cancer cells. ATP be released from cells via both nonspecific pathways. A non-regulated release occurs dying damaged cells, whereas active involves exocytotic granules, plasma membrane-derived microvesicles, ATP-binding cassette (ABC) transporters membrane channels (connexin hemichannels, pannexin 1 (PANX1), calcium homeostasis modulator (CALHM1), volume-regulated anion (VRACs) maxi-anion (MACs)). Extracellular acts at P2 purinergic receptors, among which P2X7R a key mediator final ATP-dependent biological effects. Over years, receptor- ecto-nucleotidase-targeting for therapy has been proposed actively investigated, while comparatively fewer studies have explored suitability TME as target. In this review, we briefly summarize available evidence suggesting that central role in determining fate is, therefore, suitable target therapy.

Language: Английский

Citations

188
Purinergic signaling, DAMPs, and inflammation DOI
Francesco Di Virgilio, Alba Clara Sarti, Robson Coutinho‐Silva

et al.

AJP Cell Physiology, Journal Year: 2020, Volume and Issue: 318(5), P. C832 - C835

Published: March 11, 2020

Danger sensing is one of the most fundamental evolutionary features enabling multicellular organisms to perceive potential threats, escape from risky situations, fight actual intruders, and repair damage. Several endogenous molecules are used "signal damage," currently referred as "alarmins" or "damage-associated molecular patterns" (DAMPs), being already present within all cells (preformed DAMPs), thus ready be released, others neosynthesized following injury. Over recent years it has become overwhelmingly clear that adenosine 5'-triphosphate (ATP) a ubiquitous extremely efficient DAMP (thus promoting inflammation), its main metabolite, adenosine, strong immunosuppressant dampening inflammation). Extracellular ATP ligates activates P2 purinergic receptors (P2Rs) then degraded by soluble plasma membrane ecto-nucleotidases generate acting at P1 (P1Rs). ATP, P2Rs, ecto-nucleotidases, P1Rs basic elements signaling network pillars inflammation.

Language: Английский

Citations

184
Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy DOI Creative Commons
Huailiang Wu, Yue Gong, Peng Ji

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: April 27, 2022

Abstract Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of metabolism, our understanding in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness antimetabolites for enhancing immunotherapy. A growing body evidence now supports concept that targeting increase antitumor response by (1) activating host systems via maintaining concentrations several important metabolites, such as adenosine ATP, (2) promoting immunogenicity caused increased mutability genomic instability disrupting purine pyrimidine pool, (3) releasing nucleoside analogs microbes to regulate immunity. Therapeutic approaches combined with immunotherapy have achieved exciting success preclinical animal models. Here, we review how dysregulated promote growth interact system, provide future insights into immunotherapeutic treatment various malignancies.

Language: Английский

Citations

111
Targeted P2X7/NLRP3 signaling pathway against inflammation, apoptosis, and pyroptosis of retinal endothelial cells in diabetic retinopathy DOI Creative Commons
Hui Kong, Hongran Zhao, Tianran Chen

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(4)

Published: April 12, 2022

Abstract Retinal endothelial cells (RECs) are the primary target for diabetes-induced vascular damage. The P2X7/NLRP3 pathway plays an essential role in amplifying inflammation via ATP feedback loop, promoting inflammatory response, pyroptosis, and apoptosis of RECs early stages diabetic retinopathy induced by hyperglycemia inflammation. 3TC, a type nucleoside reverse transcriptase inhibitor, is effective against inflammation, as it can targeting formation P2X7 large pore formation. Hence, our aim was to evaluated anti-inflammatory effects potential mechanisms action 3TC vitro retinal microvascular treated with high-glucose (HG) lipopolysaccharide (LPS), well vivo retinas C57BL/6J male mice streptozotocin-induced diabetes. expression inflammasome-related proteins NLRP3, 3TC-treated were compared those untreated mice. Furthermore, anti-inflammatory, anti-apoptotic, anti-pyroptotic cultured cells. Co-application HG LPS significantly increased secretion IL-6, IL-1β, TNF-α, levels, whereas decreased cell apoptosis, pyroptosis. Inhibition P2X7R NLRP3 inflammasome activation inflammasome-mediated injury. prevented cytokine release following co-application LPS/BzATP. Our findings provide new insights regarding environment-induced injury, including

Language: Английский

Citations

96
Mitigation of chilling injury in mango fruit by methyl jasmonate is associated with regulation of antioxidant capacity and energy homeostasis DOI
Ting Huang,

Gangshuai Liu,

Lisha Zhu

et al.

Postharvest Biology and Technology, Journal Year: 2024, Volume and Issue: 211, P. 112801 - 112801

Published: Jan. 28, 2024

Language: Английский

Citations

32
Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance DOI Creative Commons
Tommaso Scolaro, Marta Manco, Mathieu Pecqueux

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(8), P. 1206 - 1226

Published: June 6, 2024

Many individuals with cancer are resistant to immunotherapies. Here, we identify the gene encoding pyrimidine salvage pathway enzyme cytidine deaminase (CDA) among top upregulated metabolic genes in several immunotherapy-resistant tumors. We show that CDA cells contributes uridine diphosphate (UDP) pool. Extracellular UDP hijacks immunosuppressive tumor-associated macrophages (TAMs) through its receptor P2Y

Language: Английский

Citations

23
The Urothelium: Life in a Liquid Environment DOI
Marianela G. Dalghi, Nicolás Montalbetti, Marcelo D. Carattino

et al.

Physiological Reviews, Journal Year: 2020, Volume and Issue: 100(4), P. 1621 - 1705

Published: March 19, 2020

The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment communicates changes to underlying tissues including afferent nerve fibers smooth muscle. goal of this review is summarize new insights into urothelial biology function have occurred in past decade. After familiarizing reader with key aspects histology, we describe development regeneration. This followed by an extended discussion function, information about roles glycocalyx, ion water transport, tight junctions, cellular tissue shape other adaptations accompany expansion contraction lower tract. We also explore evidence urothelium can alter solute composition urine during normal physiology response overdistension. complete providing overview our current knowledge environment, discussing sensor transducer functions exploring role circadian rhythms gene expression, describing novel research tools are likely further advance understanding biology.

Language: Английский

Citations

135
Physiological stress response of the scleractinian coral Stylophora pistillata exposed to polyethylene microplastics DOI
Chantal M. Lanctôt, Vanessa N. Bednarz, Steven D. Melvin

et al.

Environmental Pollution, Journal Year: 2020, Volume and Issue: 263, P. 114559 - 114559

Published: April 12, 2020

Language: Английский

Citations

87
The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications DOI Open Access
John Charles Rotondo, Chiara Mazziotta,

Carmen Lanzillotti

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1116 - 1116

Published: Feb. 22, 2022

The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to variety of cellular processes, while its dysregulation linked inflammation and cancer. P2X7R expressed in cancer immune system cell surfaces. ATP plays key role numerous metabolic processes due abundance the tumour microenvironment. an important by interacting with ATP. unusual property that stimulation low doses causes opening permeable channel for sodium, potassium, calcium ions, whereas sustained high favours formation non-selective pore. latter effect induces change intracellular homeostasis leads death. This evidence suggests both pro- anti-tumour proprieties. increasingly recognised as regulator inflammation. In this review, we aimed describe most relevant characteristics function, activation, ligands, also summarising activation context currently used therapeutic approaches clinical trials modulators are described.

Language: Английский

Citations

65
Signalling by extracellular nucleotides in health and disease DOI Creative Commons
Valentina Vultaggio-Poma, Simonetta Falzoni,

Giada Salvi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2022, Volume and Issue: 1869(5), P. 119237 - 119237

Published: Feb. 9, 2022

Nucleotides are released from all cells through regulated pathways or as a result of plasma membrane damage cell death. Outside the cell, nucleotides act signalling molecules triggering multiple responses via specific receptors P2 family. In nervous system, purinergic has key function in neurotransmission. is one major modulators basal tissue homeostasis, while its dysregulation contributes to pathogenesis various disease, including inflammation and cancer. Pre-clinical clinical evidence shows that selective agonists antagonists effective treatments for many pathologies, thus highlighting relevance extracellular therapeutic targets.

Language: Английский

Citations

42