Department of Pharmacology, Kochi Medical School, Kochi University, Kohasu, Okoh-cho, Nankoku 783-8505, Japan.
Int J Mol Sci. 2021 Jul 21;22(15):7765. doi: 10.3390/ijms22157765.
Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn chelator for the maintenance of Zn homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.
中风是全球范围内主要的死亡原因之一，导致严重的残疾。缺血后损伤，特别是在易发生缺血的海马体中，是一个严重的问题，因为它导致血管性痴呆。许多研究表明，在海马体中，缺血/再灌注通过氧化应激和神经元锌（Zn）稳态失调诱导神经元死亡。谷胱甘肽 (GSH) 作为一种主要的细胞内抗氧化剂，在保护神经元免受氧化应激方面起着重要作用。此外，GSH 的巯基可以作为神经元中 Zn 稳态的主要 Zn 螯合剂。这些证据表明神经元 GSH 水平可能是中风后神经元存活的关键因素。在神经元中，兴奋性氨基酸载体 1 (EAAC1) 参与半胱氨酸的内流，细胞内半胱氨酸是 GSH 合成的限速底物。最近，几项研究表明，通过 EAAC1 摄取半胱氨酸通过促进缺血动物模型中海马体 GSH 合成来抑制缺血诱导的神经元死亡。在本文中，我们旨在综述和描述 GSH 在缺血/再灌注后海马体神经保护中的作用，重点介绍 EAAC1。
