Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

Shestopalov, Valery I.; Panchin, Yu. V.; Tarasova, O. S.; Gaynullina, Dina; Kovalzon, V. M.

doi:10.3389/fncel.2017.00210

Cited by 15 publications

(12 citation statements)

References 109 publications

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“…Prostaglandin D2 receptor 2 (PTGDR2) is one of the receptors of PGD2, which was first found in type 2 helper T lymphocytes and is therefore referred to as the chemoattractant receptor molecule expressed on Th2 (CRTH2). At present, PGD2/PTGDR2 signaling research has mainly focused on sleep promotion and inflammatory response mediation . Although PGD2 has been shown to have antitumor effects for decades, studies of PGD2 on the regulation of tumor cells are limited.…”

Section: Introductionmentioning

confidence: 99%

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Zhang

Bie

et al. 2018

Stem Cells

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The antitumor effect of prostaglandin D2 (PGD2) on gastric cancer (GC) has been known for decades. However, the mechanism of PGD2's control of GC growth is unclear. Cancer stem cells (CSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. Herein, we discovered that signaling between PGD2 and its receptor (PTGDR2) has the ability to restrict the self-renewal of GC cells in vitro and suppress tumor growth and metastasis in vivo. To obtain these findings, we first determined that PGD2 synthase (L-PTGDS) and PTGDR2 expression were lower in GC tissues than adjacent tissues and was associated with the patients' prognosis. Moreover, the expression of L-PTGDS and PTGDR2 was negatively correlated with the GC-CSC markers Sall4 and Lgr5 in GC tissues. Second, L-PTGDS and PTGDR2 expression were knocked down in CSC-like cells, resulting in enhanced expression of CSC markers and self-renewal ability. Direct PGD2 stimulation and L-PTGDS overexpression produced the opposite effect. Thirdly, PGD2 inhibited tumor growth and incidence rate in a subcutaneous tumor model and suppressed liver and mesenteric metastasis in a peritoneal metastasis model. Interfering with the expression of PTGDR2 reversed these effects in vivo. Last, a mechanistic study found that PGD2 inhibited STAT3 phosphorylation and nuclear expression. Further experiments revealed that the inhibitory effect of PGD2 on the expression of CSC markers disappeared after mutations were introduced into STAT3 phosphorylation (Thr705) site. In short, this study reveals a novel function of PGD2/PTGDR2 signaling on CSC regulation and provides a new way to control the development of GC. Stem Cells 2018;36:990-1003.

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Section: Introductionmentioning

confidence: 99%

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Zhang

Bie

et al. 2018

Stem Cells

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“…In this scheme, PanX1 would participate to a negative feedback control of synaptic transmission. Such a mechanism would provide a homeostatic regulation of neuronal transmission in the cerebellum, as has recently been suggested elsewhere [51]. The presence of PanX1 in Zebrin II-positive regions could thus help neurons adapt to the increased activity observed in these microzones.…”

Section: Discussionmentioning

confidence: 68%

Patterned expression of Pannexin 1 channels in the adult cerebellar Purkinje cells

Meunier

Lévénès

Ady

et al. 2018

Preprint

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18 19 Pannexin1 (PanX1) are recently discovered proteins that can form large pore 20 channels at the cell surface. They have been implicated in ATP-dependent cell-to-cell 21 communication and in several pathophysiological processes such as inflammation, 22 cell death and epilepsy. Using immunohistochemistry in the adult mouse, we 23 describe the presence of PanX1 in the deep cerebellar nuclei, in large cells of the 24 granular layer, presumably Golgi interneurones, in some Bergmann glia radial 25 processes as well as in the soma and dendrites of Purkinje cells. In the latter, PanX1, 26 like many other proteins, distribute heterogeneously. Only Zebrin II-positive Purkinje 27 cells express PanX1, in accordance with the so-called "zebra-striped" modular 28 architecture of the cerebellum. This distribution in zebra-stripes suggest that PanX1 29 may contribute to the control of ensemble activity within cerebellar microdomains or 30 to the response of Purkinje cell to excitotoxicity and cell-death messages. 31 32

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“…Novel research proposals describe the role of pannexins (glycoproteins that are able to form single-membrane channels) in the control of sleep. Pannexin-1 (Panx1) hemichannels may influence sleep homeostasis by modulating the release of ATP (which further interacts with adenosine and other somnogenic cytokines) and by their vasorelaxation effects, which regulate cerebral blood flow (39). Recent evidence shows that the lateral habenula is another oscillator besides SCN, which may be able to express intrinsic circadian properties.…”

Section: Circadian and Homeostatic Control Of Sleepmentioning

confidence: 99%

Neurobiology of sleep (Review)

et al. 2021

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Sleep is a physiological global state composed of two different phases: Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The control mechanisms of sleep manifest at the level of genetic, biological and cellular organization. Several brain areas, including the basal forebrain, thalamus, and hypothalamus, take part in regulating the activity of this status of life. The signals between different brain regions and those from cortical areas to periphery are conducted through various neuromediators, which are known to either promote wakefulness or sleep. Among others, serotonin, norepinephrine, histamine, hypocretin (orexin), acetylcholine, dopamine, glutamate, and gamma-aminobutyric acid are known to orchestrate the intrinsic mechanisms of sleep neurobiology. Several models that explain the transition and the continuity between wakefulness, NREM sleep and REM sleep have been proposed. All of these models include neurotransmitters as ligands in a complex reciprocal connectivity across the key-centers taking part in the regulation of sleep. Moreover, various environmental cues are integrated by a central pacemaker-located in the suprachiasmatic nucleus-which is able to connect with cortical regions and with peripheral tissues in order to promote the sleep-wake pattern. Contents

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Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

Cited by 15 publications

References 109 publications

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Patterned expression of Pannexin 1 channels in the adult cerebellar Purkinje cells

Neurobiology of sleep (Review)

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