Effect of SCH442416 on glutamate uptake in retinal Muller cells at increased hydrostatic pressure
Effect of SCH442416 on glutamate uptake in retinal Muller cells at increased hydrostatic pressure
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SCH442416 在静水压升高时对视网膜 Muller 细胞谷氨酸摄取的影响
DOI：
10.3892/mmr.2015.3882
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发表时间：
2015-09-01
影响因子：
3.4
通讯作者：
Zhong, Yisheng
中科院分区：
文献类型：
--
作者：
Li, Yong;Liu, Xiaohong;Zhong, Yisheng
A(2A)受体(A(2A)AR)拮抗剂被认为是改善神经系统疾病治疗的一个有吸引力的选择，A(2A)R拮抗剂的作用可能是抑制谷氨酸的释放，防止神经元损伤。本研究的目的是探讨SCH442416是否能调节静水压力增加时视网膜Muller细胞对谷氨酸的摄取。用逆转录-定量聚合酶链式反应和免疫印迹法检测视网膜Muller细胞在40 mm Hg压力下24 h谷氨酰胺合成酶(GS)和谷氨酸转运体(GLAST)的水平，并用闪烁计数法测定细胞摄取谷氨酸的能力。用100 nM SCH442416处理Muller细胞，在40 mm Hg压力下处理24 h，观察GS和GLAST的mRNA和蛋白表达水平以及谷氨酸摄取活性。在40 mm Hg压力下，Muller细胞中OS和GLAST的表达水平及谷氨酸摄取活性均显著降低。SCH442416可明显改善40 mm Hg压力下视网膜Muller细胞GS和GLAST表达水平的下降，提高细胞对谷氨酸的摄取活性，导致压力下Muller细胞GS和GLAST表达水平升高，谷氨酸摄取活性增强。这些结果表明，SCH442416可能是一种潜在的神经保护剂，通过促进细胞外谷氨酸的清除来治疗青光眼。
The A(2A), receptor (A(2A)AR) antagonist has been considered as an attractive option to improve the treatment of neurological disorders, and the function of A(2A)R 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 Muller cells under increased hydrostatic pressure. The levels of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) were assessed in retinal Muller 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 Muller cells with 100 nM SCH442416 under 40 mmHg pressure br 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 OS and GLAST in the Muller 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 Muller cells exposed to 40 mmHg pressure, resulting in increased expression levels of GS and GLAST, and increased glutamate uptake activity in the Muller 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.