Lu Li, Zhang Guangru, Song Chunli, Wang Xuexi, Qian Weina, Wang Zhuanling, Liu Yanan, Gong Sheng, Zhou Shuning
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu, China.
Qinghai Hospital of Traditional Chinese medicine, Xining 810000, Qinghai, China.
Neurosci Lett. 2017 Jan 1;636:241-247. doi: 10.1016/j.neulet.2016.11.034. Epub 2016 Nov 16.
Polyunsaturated fatty acids (PUFAs) have neuroprotective effects against ischemic brain diseases. The newly discovered potassium channel "TREK-1" is a promising target for therapies against neurodegeneration. Arachidonic acid (AA) is an n-6 PUFA, as well as a potent TREK-1 activator. We previously showed that TREK-1 is expressed at high levels in astrocytes. However, the effect of AA on astrocytes in ischemia remains unknown. Here, we assessed the effects of 3-30μM AA on astrocyte apoptosis, glutamate uptake, and expression of the astrocytic glutamate transporter 1 (GLT-1) and TREK-1 under different conditions. Under normal conditions, 3-30μM AA showed no effect on astrocytic apoptosis or TREK-1 expression, whereas glutamate uptake decreased significantly and its change paralleled the decreased expression of GLT-1. When astrocytes were subjected to 4h of oxygen-glucose deprivation (OGD), 10μM AA markedly alleviated OGD-induced cell death, recovering from 63.50±1.90% to 82.96±4.63% of the control value. AA also rescued the decreased glutamate uptake and increased mRNA, as well as protein levels of GLT-1 and TREK-1. Our results provide new evidence of a protective effect of AA on astrocytes under OGD conditions, suggesting that a low concentration of AA may protect against brain ischemic diseases.
多不饱和脂肪酸（PUFAs）对缺血性脑疾病具有神经保护作用。新发现的钾通道“TREK-1”是神经退行性疾病治疗的一个有前景的靶点。花生四烯酸（AA）是一种n-6多不饱和脂肪酸，也是一种有效的TREK-1激活剂。我们之前表明TREK-1在星形胶质细胞中高水平表达。然而，AA在缺血状态下对星形胶质细胞的影响仍不清楚。在此，我们评估了3 - 30μM AA在不同条件下对星形胶质细胞凋亡、谷氨酸摄取以及星形胶质细胞谷氨酸转运体1（GLT-1）和TREK-1表达的影响。在正常条件下，3 - 30μM AA对星形胶质细胞凋亡或TREK-1表达无影响，而谷氨酸摄取显著降低，其变化与GLT-1表达降低平行。当星形胶质细胞经历4小时氧糖剥夺（OGD）时，10μM AA显著减轻OGD诱导的细胞死亡，从对照值的63.50±1.90%恢复到82.96±4.63%。AA还挽救了降低的谷氨酸摄取以及GLT-1和TREK-1的mRNA和蛋白质水平的增加。我们的结果为AA在OGD条件下对星形胶质细胞的保护作用提供了新证据，表明低浓度的AA可能预防脑缺血疾病。
