TRPV4: Molecular Conductor of a Diverse Orchestra

Physiological Reviews, Journal Year: 2016, Volume and Issue: 96(3), P. 911 - 973

Published: June 2, 2016

Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led Schultz (Nat Cell Biol 2: 695-702, 2000) and Liedtke (Cell 103: 525-535, 2000). TRPV4 now recognized as being polymodal ionotropic that activated disparate array of stimuli, ranging from hypotonicity to heat acidic pH. Importantly, this ion channel constitutively expressed capable spontaneous activity the absence agonist stimulation, which suggests it serves important physiological functions, does its widespread dissemination throughout body capacity interact with other proteins. Not surprisingly, therefore, has emerged more recently fulfills great number roles various disease states are attributable absence, or abnormal functioning, channel. Here, we review known characteristics channel's structure, localization function, including activators, examine functional importance health disease.

Language: Английский

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ATP release through pannexon channels

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 370(1672), P. 20140191 - 20140191

Published: May 26, 2015

Extracellular adenosine triphosphate (ATP) serves as a signal for diverse physiological functions, including spread of calcium waves between astrocytes, control vascular oxygen supply and ciliary beat in the airways. ATP can be released from cells by various mechanisms. This review focuses on channel-mediated release its main enabler, Pannexin1 (Panx1). Six subunits Panx1 form plasma membrane channel termed ‘pannexon’. Depending mode stimulation, pannexon has large conductance (500 pS) unselective permeability to molecules less than 1.5 kD or is small (50 pS), chloride-selective channel. Most pathological stimuli induce conformation, whereas conformation so far only been observed with exclusive voltage activation The interaction pannexons intimate. not conduit ATP, permitting efflux down concentration gradient, but also modulated ATP. activated through both ionotropic P2X well metabotropic P2Y purinergic receptors. In absence mechanism, this positive feedback loop would lead cell death owing linkage receptors apoptotic processes. A mechanism preventing excessive provided binding (with low affinity) protein gating shut.

Language: Английский

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Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Nature Reviews Rheumatology, Journal Year: 2016, Volume and Issue: 13(1), P. 41 - 51

Published: Nov. 10, 2016

Language: Английский

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The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants, Journal Year: 2019, Volume and Issue: 8(5), P. 121 - 121

Published: May 5, 2019

Astrocytes outnumber neurons in the human brain, and they play a key role numerous functions within central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis neurogenesis, synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal vascular systems, leading to clearance of disease-specific protein aggregates, such as β-amyloid, α-synuclein. The astrocytic big conductance K+ (BK) channel plays these processes. Recently, potential therapeutic agents that target have been tested for their brain. In this review, we discuss BK antioxidant heme oxygenase metabolites following injury. A better understanding cellular molecular mechanisms astrocytes’ healthy diseased brains will greatly contribute development approaches Alzheimer’s disease, Parkinson’s stroke.

Language: Английский

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Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 93, P. 101169 - 101169

Published: Feb. 1, 2023

Language: Английский

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Independent origins of neurons and synapses: insights from ctenophores

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 371(1685), P. 20150041 - 20150041

Published: Nov. 24, 2015

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits achieve similar functional outcomes. Genomics metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal pan-synaptic genes across metazoans, including remarkable examples lineage-specific evolution neurogenic molecules as well synaptic components. Sponges placozoans are two lineages without muscular systems. The possibility secondary loss neurons synapses Porifera/Placozoa clades a highly unlikely less parsimonious scenario. We conclude acetylcholine, serotonin, histamine, dopamine, octopamine gamma-aminobutyric acid (GABA) were recruited transmitters systems cnidarian bilaterian lineages. By contrast, numerous secretory peptides, indicating extensive adaptations within clade suggesting early might be peptidergic. Comparative analysis glutamate also shows innovations, implying this ubiquitous metabolite intercellular messenger over course convergent parallel mechanisms communication. Therefore: (i) we view neuron character but not genetic character, (ii) any given system cannot considered single because it composed cell with distinct genealogies, origins evolutionary histories. Thus, when reconstructing nervous systems, ought start identification particular by establishing distant homologies or evolution. In corollary independent neurons, our analyses both electrical chemical once.

Language: Английский

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Neuronal P2X7 Receptors Revisited: Do They Really Exist?

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 37(30), P. 7049 - 7062

Published: July 26, 2017

P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein–protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling transition from nonselective ion channel mode membrane pore allowing passage large molecules. There an ongoing dispute existence neuronal with consequences for our knowledge involvement neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, various neurodegenerative diseases. Whereas early results appeared support operation at neurons, more recently glial are increasingly considered as indirect causes effects. Specific tools limited value because poor selectivity agonists, inherent failure antibodies differentiate between number active inactive splice variants, or gain-of-function loss-of-function small nucleotide polymorphisms receptor. Unfortunately, available P2RX7 knock-out mice generated by pharmaceutical companies possess certain which evade inactivation. In view discovered bidirectional dialogue astrocytes neurons (and even microglia neurons), we offer alternative explanation previous data, assumedly neurons. We think that unbiased reader will follow argumentation astrocytic microglial being primary targets pathologically high extracellular ATP concentrations, although localization these cannot be fully excluded either.

Language: Английский

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Inducible rodent models of glaucoma

Progress in Retinal and Eye Research, Journal Year: 2019, Volume and Issue: 75, P. 100799 - 100799

Published: Sept. 23, 2019

Language: Английский

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The P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Exposed to Mechanical Strain

Frontiers in Cellular Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: Aug. 8, 2017

Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune and can link insult to chronic inflammation. requires two stages contribute: priming activation. stage involves upregulation components while activation results assembly complex. step be rate limiting connect inflammation, but our knowledge signals that regulate sterile inflammation limited. This study examined between mechanical strain systems. Transient non-ischemic elevation intraocular pressure increased mRNA for IL-1β, NLRP3, ASC, CASP1 rat mouse retinas. was greater 1 day after insult, rise IL-1β most pronounced. P2X7 receptor implicated mechanosensitive vivo, as antagonist Brilliant Blue G (BBG) blocked expression, agonist BzATP mimicked pressure-dependent absent knockout mice. In vitro measurements optic nerve head astrocytes demonstrated expression following stretch or swelling. increase eliminated by degradation extracellular ATP apyrase, block pannexin hemichannels carbenoxolone, probenecid, 10panx1 peptide. also antagonists BBG, A839977 A740003. prevented blocking transcription factor NFκB Bay 11-7082, swelling-dependent fall inhibitor IκB-α reduced summary, trauma retina primed components, only if there release through hemichannels, autostimulation receptor. As trigger activation, may have central linking neuroinflammation.

Language: Английский

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Purines in the eye: Recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

Experimental Eye Research, Journal Year: 2014, Volume and Issue: 127, P. 270 - 279

Published: Aug. 20, 2014

This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands cross-talk between P2X7 receptors both M3 muscarinic α1D-adrenergic can influence tear secretion. In cornea, lead to post-translational modification EGFR structural proteins participate wound repair epithelium expression matrix stroma. Purines act at on trabecular meshwork ciliary intraocular pressure (IOP); ATP-release pathways inflow outflow cells differ, possibly permitting differential modulation adenosine delivery. Modulators cell ATP release include volume, stretch, extracellular Ca2+ concentration, oxidation state, actin remodeling endogenous cardiotonic steroids. lens, osmotic stress leads following TRPV4 activation upstream hemichannel opening. anterior eye, diadenosine polyphosphates such as Ap4A P2 rate composition secretion, impact corneal healing lower IOP. The Gq11-coupled P2Y1-receptor contributes volume control Müller thus retina. P2X are expressed neurons inner outer retina contribute visual processing well demise retinal ganglion cells. RPE cells, balance may lysosomal pH lipofuscin formation. optic nerve head astrocytes, mechanosensitive via pannexin hemichannels, coupled with stretch-dependent upregulation pannexins, provides a mechanism for signaling chronic glaucoma. With so many linked divergent functions throughout ensuring transmitters remain local stimulation is restricted intended target be key issue understanding becomes pathological disease.

Language: Английский

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