Pannexin-1 Channel Regulates ATP Release in Epilepsy

Shan, Yisi; Ni, Yaohui; Gao, Zhiwei

doi:10.1007/s11064-020-02981-9

Cited by 12 publications

(8 citation statements)

References 67 publications

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“…iScience 24, 103478, December 17, 2021 iScience Article ATP and its metabolites have become a critical component of multiple diseases, including HIV and COVID-19 (Abouelkhair, 2020;Alves et al, 2020;de Oliveira et al, 2021;Dos Anjos et al, 2020;Edwards, 2021;Fonteles et al, 2020;Franciosi et al, 2021;Klaver and Thurnher, 2021;Mishra et al, 2021;Pacheco and Faria, 2021;Shan et al, 2020;Simoes and Bagatini, 2021). Our data in long-term HIV-infected individuals indicate that several chronic effects of HIV are correlated with ATP dysfunction and vascular disease, such as cognitive impairment (Velasquez et al, 2020).…”

Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE 2 , and IL-1b release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE 2 , and IL-1b levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.

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Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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“…The excitability of primary sensory neurons is pathologically enhanced following tissue injury and inflammation [ 67 ]. Recent investigations have indicated that pharmacological inhibition or genetic deletion of Panx1 strongly attenuated the excitability of CA1 pyramidal neurons [ 68 ] and ATP release in hippocampal slices [ 69 ], suggesting that Panx1 might also reduce the nociceptive threshold by affecting the transmission and persistence of such excitability in peripheral neuralgia. The present study data showed that Panx1 deletion reduced basal inward currents in both Neuro2a cells and DRGNs during neuronal differentiation, while current densities also decreased after Panx1 blockade by 1 mmol/L Pbcd.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain

Xing,

Cibelli,

Yang

et al. 2024

Military Med Res

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Background The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. Methods Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. Results Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca2+ responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of β-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG. Conclusions The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.

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“…However, in the other group, TCGA astrocytoma, A 2A R was negatively linked to HIF1 , ENPP1 , and pannexin, and positively correlated to ADK . Pannexins 1 transmembrane channels are involved in ATP release by inducing an increase in extracellular ATP [ 53 , 54 , 55 ]. Thus, activation of these channels induces stimulation of A 2A R via increased extracellular adenosine [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma

Rafii

Ghouzlani

Naji

et al. 2023

IJMS

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Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas.

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Pannexin-1 Channel Regulates ATP Release in Epilepsy

Cited by 12 publications

References 67 publications

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain

A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma

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