Glutamate–aspartate transporter 1 attenuates oxygen–glucose deprivation‐induced injury by promoting glutamate metabolism in primary cortical neurons
Glutamate–aspartate transporter 1 attenuates oxygen–glucose deprivation‐induced injury by promoting glutamate metabolism in primary cortical neurons
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谷氨酸-天冬氨酸转运蛋白 1 通过促进初级皮质神经元中的谷氨酸代谢来减轻氧-葡萄糖剥夺引起的损伤
DOI：
10.1002/jcp.30768
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Zhen Chai
中科院分区：
文献类型：
--
作者：
Yun-Zhi Zhao;Jun Wei;Ke-Xin Song;Chen Zhou;Zhen Chai
缺血性脑卒中是一种常见的脑部疾病。然而，该疾病的治疗方法有限。达乌尔黄鼠（Spermophilus dauricus）是一种冬眠的哺乳动物，对缺血具有高度耐受性。在本研究中，GS神经元在非冬眠状态下被发现更耐氧-葡萄糖剥夺（OGD），在体外缺血模型。我们利用GS和大鼠耐力的差异来研究GS神经元对缺血的抵抗机制。我们首先确定谷氨酸-天冬氨酸转运蛋白1（GLAST）作为一种细胞保护因子，有助于GS神经元对OGD损伤的耐受性。GLAST在GS神经元的表达明显高于大鼠神经元。GLAST的过表达挽救了大鼠神经元的活力，并且GS神经元在OGD条件下GLAST敲低后表现出活力降低。从机制上讲，GLAST过表达后，更多的谷氨酸被转运到神经元中，并作为ATP产生的底物。此外，真核转录起始因子4 E结合蛋白1下调GLAST，以挽救神经元的活力。我们的研究结果不仅揭示了冬眠哺乳动物生存的重要分子机制，而且表明神经元GLAST可能是缺血性卒中治疗的潜在靶点。
Ischemic stroke is a common cerebral disease. However, the treatment for the disease is limited. Daurian ground squirrel (GS; Spermophilus dauricus), a hibernating mammalian species, is highly tolerant to ischemia. In the present study, GS neurons in a non-hibernating state were found to be more resistant to oxygen-glucose deprivation (OGD), an ischemic model in vitro. We leveraged the differences in the endurance capacity of GS and rats to investigate the mechanisms of resistance to ischemia in GS neurons. We first identified glutamate-aspartate transporter 1 (GLAST) as a cytoprotective factor that contributed to tolerance against OGD injury of GS neurons. The expression of GLAST in GS neurons was much higher than that in rat neurons. Overexpression of GLAST rescued viability in rat neurons, and GS neurons exhibited decreased viability following GLAST knockdown under OGD conditions. Mechanistically, more glutamate was transported into neurons after GLAST overexpression and served as substrates for ATP production. Furthermore, eukaryotic transcription initiation factor 4E binding protein 1 was downregulated by GLAST to rescue neuronal viability. Our findings not only revealed an important molecular mechanism underlying the survival of hibernating mammals but also suggested that neuronal GLAST may be a potential target for ischemic stroke therapy.
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影响因子：
6.3
作者：
E. Olstad;H. Qu;U. Sonnewald
通讯作者：
E. Olstad;H. Qu;U. Sonnewald
DOI：
10.1016/s0749-4041(08)79111-5
发表时间：
2009
期刊：
Yearbook of Vascular Surgery
影响因子：
--
作者：
G. Moneta
通讯作者：
G. Moneta
DOI：
10.3410/f.1023260.266688
发表时间：
2005-01
期刊：
--
影响因子：
--
作者：
G. Pier
通讯作者：
G. Pier
DOI：
10.1046/j.1460-9568.2001.01367.x
发表时间：
2001
期刊：
The European journal of neuroscience
影响因子：
--
作者：
V. Rao;A. Dogan;K. Bowen;K. Todd;R. Dempsey;R. Dempsey
通讯作者：
V. Rao;A. Dogan;K. Bowen;K. Todd;R. Dempsey;R. Dempsey
DOI：
10.1152/ajpregu.2001.281.2.r572
发表时间：
2001-08
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
--
作者：
Ø. Tøien;K. Drew;M. L. Chao;M. Rice
通讯作者：
Ø. Tøien;K. Drew;M. L. Chao;M. Rice