Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes mediated through enhancement of potassium channel TREK-1 activity

作者:Lu, Li; Zhang, Guangru; Song, Chunli; Wang, Xuexi*; Qian, Weina; Wang, Zhuanling; Liu, Yanan; Gong, Sheng; Zhou, Shuning
来源:Neuroscience Letters, 2017, 636: 241-247.
DOI:10.1016/j.neulet.2016.11.034

摘要

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 3-30 mu M 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, 3-30 mu M 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 4 h of oxygen-glucose deprivation (OGD), 10 mu M 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.