Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis Through the Akt and PERK Pathways
Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABA receptor agonist of RGCs against hypoxia-induced a...
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Published in | Frontiers in cellular neuroscience Vol. 10; p. 255 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
04.11.2016
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABA
receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl
) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl
with or without baclofen treatment, and RNA interference techniques were used to knock down the GABA
2 gene in the primary RGCs. The viability and apoptosis of RGCs were assessed using cell viability and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, Hoechst staining, and flow cytometry. The expression of cleaved caspase-3, bcl-2, bax, Akt, phospho-Akt, protein kinase RNA (PKR)-like ER kinase (PERK), phospho-PERK, eIF2α, phospho-eIF2α, ATF-4 and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured using western blotting. GABA
2 mRNA expression was determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Our study revealed that CoCl
significantly induced RGC apoptosis and that baclofen reversed these effects. CoCl
-induced reduction of Akt activity was also reversed by baclofen. Baclofen prevented the activation of the PERK pathway and the increase in CHOP expression induced by CoCl
. Knockdown of GABA
2 and the inactivation of the Akt pathway by inhibitors reduced the protective effect of baclofen on CoCl
-treated RGCs. Taken together, these results demonstrate that baclofen protects RGCs from CoCl
-induced apoptosis by increasing Akt activity and by suppressing the PERK pathway and CHOP activation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Nicola Berretta, Fondazione Santa Lucia (IRCCS), Italy; Ulkan Kilic, Istanbul Medipol University, Turkey Edited by: James Francis Curtin, Dublin Institute of Technology, Ireland |
ISSN: | 1662-5102 1662-5102 |
DOI: | 10.3389/fncel.2016.00255 |