title: Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes mediated through enhancement of potassium channel TREK-1 activity.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Qinghai Hospital of Traditional Chinese medicine, Xining 810000, Qinghai, China.
authors.forename: Guangru
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu, China; Qinghai Provincial People's Hospital, Xining 810000, Qinghai, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Song
authors.affiliation: Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou 730000, China. Electronic address: wangxuexi@lzu.edu.cn.
authors.forename: Xuexi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou 730000, China; The First Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang 712000, Shaanxi, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Qian
authors.affiliation: Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou 730000, China.
authors.forename: Zhuanling
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou 730000, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Gong
authors.affiliation: Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou 730000, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D016718:Arachidonic Acid; D005947:Glucose; D010100:Oxygen
keywords: Arachidonic acid; Astrocytes; Oxygen-glucose deprivation; TREK-1