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Abstract #61425 Published in IGR 17-1
Effect of SCH442416 on glutamate uptake in retinal Müller cells at increased hydrostatic pressure
Li Y; Liu X; Huang S; Huang P; Zhong YMolecular medicine reports 2015; 12: 3993-3998
The A2A receptor (A2AR) antagonist has been considered as an attractive option to improve the treatment of neurological disorders, and the function of A2AR antagonist may inhibit the release of glutamate and prevent neuron damage. The aim of the present study was to investigate whether SCH442416 can modulate the glutamate uptake in retinal Müller cells under increased hydrostatic pressure. The levels of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) were assessed in retinal Müller cells under 40 mmHg pressure for 24 h using reverse transcription‑quantitative polymerase chain reaction and western blotting, and a glutamate uptake assay was performed using a scintillation counting method. Following treatment of the Müller cells with 100 nM SCH442416 under 40 mmHg pressure for 24 h, the mRNA and protein expression levels of GS and GLAST, and glutamate uptake activity were investigated. Under 40 mmHg pressure, the expression levels of GS and GLAST in the Müller cells, and glutamate uptake activity were significantly reduced. Treatment with SCH442416 significantly ameliorated the decreased expression levels of GS and GLAST, and improved the glutamate uptake activity in the retinal Müller cells exposed to 40 mmHg pressure, resulting in increased expression levels of GS and GLAST, and increased glutamate uptake activity in the Müller cells under pressure. These results suggested that SCH442416 may be a potential candidate as a beneficial neuroprotective agent for the treatment of glaucoma by accelerating the clearance of extracellular glutamate.
Department of Ophthalmology, Tongren Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai 200336, P.R. China.
Full articleClassification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
11.8 Neuroprotection (Part of: 11 Medical treatment)
