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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Cell+Neurosci
2016 ; 10
(ä): 255
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Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical
Hypoxia-Induced Apoptosis Through the Akt and PERK Pathways
#MMPMID27867349
Fu P
; Wu Q
; Hu J
; Li T
; Gao F
Front Cell Neurosci
2016[]; 10
(ä): 255
PMID27867349
show ga
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(B) receptor agonist of RGCs against hypoxia-induced apoptosis.
Cobalt chloride (CoCl(2)) was applied to mimic hypoxia. Primary rat RGCs were
subjected to CoCl(2) with or without baclofen treatment, and RNA interference
techniques were used to knock down the GABA(B)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, eIF2?, phospho-eIF2?, ATF-4 and CCAAT/enhancer-binding protein
homologous protein (CHOP) were measured using western blotting. GABA(B)2 mRNA
expression was determined using quantitative real-time polymerase chain reaction
(qRT-PCR) analysis. Our study revealed that CoCl(2) significantly induced RGC
apoptosis and that baclofen reversed these effects. CoCl(2)-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(2).
Knockdown of GABA(B)2 and the inactivation of the Akt pathway by inhibitors
reduced the protective effect of baclofen on CoCl(2)-treated RGCs. Taken
together, these results demonstrate that baclofen protects RGCs from
CoCl(2)-induced apoptosis by increasing Akt activity and by suppressing the PERK
pathway and CHOP activation.