Relative Role of Akt, ERK and CREB in Alcohol-Induced Microglia P2X4R Receptor Expression

Overview

Journal Alcohol Alcohol

Publisher Oxford University Press

Specialty Psychiatry

Date 2016 Mar 7

PMID 26946194

Citations 14

Authors

Larisa Gofman

Nicole C Fernandes

Raghava Potula

Affiliations

Soon will be listed here.

Abstract

Aims: Previously we have demonstrated altered microglia P2X4R expression in response to alcohol and pharmacological blockade with a selective P2X4R antagonist can reverse the action, suggesting that P2X4R play a role in mediating alcohol-induced effects on microglia. In the present study, we investigated the underlying signaling mediators, which may play a role in modulating P2X4R expression in microglia cells in response to alcohol.

Methods: Embryonic stem cell-derived microglia (ESdM) cells were used to investigate the potential mechanisms involved in the regulation of P2X4R in response to alcohol. Selective P2X4R antagonist and kinase inhibitors were used to further corroborate the signal transduction pathway through which alcohol modulates P2X4R expression in microglia.

Results: Alcohol (100 mM) suppressed phosphorylated AKT and ERK cascades in native ESdM cells. This alcohol-induced suppression was confirmed to be P2X4R-dependent through the use of a selective P2X4R antagonist and knockdown of P2XR4 by siRNA. Alcohol increased transcriptional activity of CREB. P2X4R antagonist blocked alcohol-induced effects on CREB, suggesting a P2X4R-mediated effect.

Conclusion: These findings provide important clues to the underlying mechanism of purinoceptors in alcohol-induced microglia immune suppression.

Citing Articles

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Decreased tubulin-binding cofactor B was involved in the formation disorder of nascent astrocyte processes by regulating microtubule plus-end growth through binding with end-binding proteins 1 and 3 after chronic alcohol exposure.

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ERK1/2 Signalling Pathway Regulates Tubulin-Binding Cofactor B Expression and Affects Astrocyte Process Formation after Acute Foetal Alcohol Exposure.

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Sophocleous R, Ooi L, Sluyter R Int J Mol Sci. 2022; 23(10).

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Wu S, Han J, Yao N, Li Y, Zhang F, Shi Y CNS Neurosci Ther. 2022; 28(7):1008-1018.

PMID: 35352488 PMC: 9160453. DOI: 10.1111/cns.13831.

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