Decreased cysteine uptake by EAAC1 gene deletion exacerbates neuronal oxidative stress and neuronal death after traumatic brain injury

被引:0
|
作者
Bo Young Choi
In Yeol Kim
Jin Hee Kim
Bo Eun Lee
Song Hee Lee
A. Ra Kho
Hee Jae Jung
Min Sohn
Hong Ki Song
Sang Won Suh
机构
[1] Hallym University,Department of Physiology
[2] College of Medicine,Department of Neurology
[3] Hallym University,Department of Nursing
[4] College of Medicine,undefined
[5] Inha University,undefined
来源
Amino Acids | 2016年 / 48卷
关键词
EAAC1; Cysteine; Zinc; TBI; Reactive oxygen species; Microglia;
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中图分类号
学科分类号
摘要
Excitatory amino acid carrier type 1 (EAAC1), a high-affinity glutamate transporter, can expend energy to move glutamate into neurons. However, under normal physiological conditions, EAAC1 does not have a great effect on glutamate clearance but rather participates in the neuronal uptake of cysteine. This process is critical to maintaining neuronal antioxidant function by providing cysteine for glutathione synthesis. Previous study showed that mice lacking EAAC1 show increased neuronal oxidative stress following transient cerebral ischemia. In the present study, we sought to characterize the role of EAAC1 in neuronal resistance after traumatic brain injury (TBI). Young adult C57BL/6 wild-type or EAAC1−/− mice were subjected to a controlled cortical impact model for TBI. Neuronal death after TBI showed more than double the number of degenerating neurons in the hippocampus in EAAC1−/− mice compared with wild-type mice. Superoxide production, zinc translocation and microglia activation similarly showed a marked increase in the EAAC1−/− mice. Pretreatment with N-acetyl cysteine (NAC) reduced TBI-induced neuronal death, superoxide production and zinc translocation. These findings indicate that cysteine uptake by EAAC1 is important for neuronal antioxidant function and survival following TBI. This study also suggests that administration of NAC has therapeutic potential in preventing TBI-induced neuronal death.
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页码:1619 / 1629
页数:10
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