Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release DOI Creative Commons
Yasunobu Okada

The Journal of Physiological Sciences, Journal Year: 2024, Volume and Issue: 74(1)

Published: June 14, 2024

The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed most vertebrate cell types, and essentially involved volume regulation after swelling the induction of death. This series review articles describes what already known remains to be uncovered about functional molecular properties as well physiological pathophysiological roles VSOR/VRAC. Part 2 article describes, from standpoints, first pivotal VSOR/VRAC release autocrine/paracrine organic signal molecules, such glutamate, ATP, glutathione, cGAMP, itaconate, second swelling-independent -dependent activation mechanisms Since pore size has now been evaluated by electrophysiological 3D-structural methods, signal-releasing activity here discussed comparing sizes these signals channel size. Swelling-independent include a physicochemical one caused reduction intracellular ionic strength biochemical oxidation due stimulation receptor agonists apoptosis inducers. Because some substances released via upon can trigger augment an autocrine fashion, swelling-dependent are divided into two phases: phase induced per se signals.

Language: Английский

How microglia contribute to the induction and maintenance of neuropathic pain DOI
Marzia Malcangio, George Sideris-Lampretsas

Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

Citations

0
Research progress in different physical therapies for treating peripheral nerve injuries DOI Creative Commons

Xiaolei Chu,

Xiaoxuan Zhao,

S.J. Liu

et al.

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

Physical therapy is gaining recognition as an effective therapeutic approach in the realm of peripheral nerve injury (PNI) research. This article seeks to provide a comprehensive review latest advancements, applications, and mechanisms action four physical modalities-ultrasound, electrical stimulation, photobiomodulation, aerobic exercise-in context PNI. Ultrasound, characterized by its mechanical thermal effects, widely regarded non-invasive or minimally invasive method for neural modulation. Electrical stimulation therapy, prevalent technique PNI treatment, entails application electric currents stimulate muscle tissues, thereby facilitating regeneration mitigating atrophy. Photobiomodulation, process that influences cell metabolism through absorption photon energy, closely associated with field rehabilitation medicine. Additionally, exercise, popular form activity, serves enhance blood circulation improve neuronal function. The discusses various methods injuries, including hyperbaric oxygen magnetic biofeedback addition traditional approaches. Despite challenges treatment persist, such need standardized protocols, consideration individual variations, assessment long-term effectiveness. Future research needed address these issues. In summary, this offers theoretical empirical evidence supporting utilization management aims promote further clinical practice field, contributing enhancing patient quality life recovery outcomes.

Language: Английский

Citations

0
Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway DOI Creative Commons
Ling Ling, Min Luo, Haolin Yin

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(22)

Published: Nov. 1, 2024

Sinomenine (SIN), a bioactive isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, is efficacious against various chronic pain conditions. Inhibition microglial activation at spinal level contributes to analgesic effects SIN. Microglial in dorsal horn key sensitising neuropathic pain. Consequently, this study aimed investigate whether antinociceptive SIN are induced through inhibition underlying mechanisms. In study, we observed that alleviated constriction injury (CCI)-induced hypersensitivity, neuroinflammation. Consistently, evoked upregulation transforming growth factor-beta1 (TGF-β1) phosphorylated Smad3 L4-6 ipsilateral CCI mice. Intrathecal injection TGF-β1 siRNA an activin receptor-like receptor (ALK5) inhibitor reversed SIN's antimicroglial on Moreover, targeting vitro with dampened inhibitory effect lipopolysaccharide-induced activation. Finally, abrogated SIN-induced relief These findings indicate TGF-β1/ALK5/Smad3 axis plays role pain, indicating its suppressive ability microglia.

Language: Английский

Citations

3
ATP-elicited Cation Fluxes Promote Volume-regulated Anion Channel LRRC8/VRAC Transport cGAMP for Antitumor Immunity DOI
Li Wang,

Limin Cao,

Zhihong Li

et al.

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 213(3), P. 347 - 361

Published: June 7, 2024

The cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex still unfolding. A new paradigm suggests that cancer cells' cGAS-synthesized cGAMP can be transferred tumor-infiltrating immune cells, eliciting STING-dependent IFN-β response for immunity. Nevertheless, how tumor microenvironment may shape this process remains unclear. In study, we found extracellular ATP, an regulatory molecule widely present in microenvironment, potentiate transfer, thereby boosting STING signaling murine macrophages fibroblasts. Notably, genetic ablation or chemical inhibition volume-regulation anion channel LRRC8/volume-regulated (VRAC), a recently identified transporter, abolished ATP-potentiated transfer response, revealing crucial role LRRC8/VRAC cross-talk ATP cGAMP. Mechanistically, activation P2X family receptors triggered Ca2+ influx K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked efflux alleviated phosphorylation VRAC's obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated S174 LRRC8A could act as checkpoint VRAC steady state rheostat responsiveness. MC38-transplanted model, systemically blocking CD39 ENPP1, hydroxylases cGAMP, respectively, elevated NK, NKT, CD8+ T cell responses restrained growth mice. Altogether, study establishes facilitating transport provides insight into harnessing

Language: Английский

Citations

2
Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release DOI Creative Commons
Yasunobu Okada

The Journal of Physiological Sciences, Journal Year: 2024, Volume and Issue: 74(1)

Published: June 14, 2024

The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed most vertebrate cell types, and essentially involved volume regulation after swelling the induction of death. This series review articles describes what already known remains to be uncovered about functional molecular properties as well physiological pathophysiological roles VSOR/VRAC. Part 2 article describes, from standpoints, first pivotal VSOR/VRAC release autocrine/paracrine organic signal molecules, such glutamate, ATP, glutathione, cGAMP, itaconate, second swelling-independent -dependent activation mechanisms Since pore size has now been evaluated by electrophysiological 3D-structural methods, signal-releasing activity here discussed comparing sizes these signals channel size. Swelling-independent include a physicochemical one caused reduction intracellular ionic strength biochemical oxidation due stimulation receptor agonists apoptosis inducers. Because some substances released via upon can trigger augment an autocrine fashion, swelling-dependent are divided into two phases: phase induced per se signals.

Language: Английский

Citations

2