EAAC1 gene deletion alters zinc homeostasis and enhances cortical neuronal injury after transient cerebral ischemia in mice

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)
Bong Geom JangSang Won Suh

Abstract

The excitatory amino acids glutamate and cysteine are actively transported into neurons from the extracellular space by the high affinity glutamate transporter EAAC1. The astrocyte glutamate transporters, GLT1 and GLAST, are the primary mediators of glutamate clearance. EAAC1 has a limited role in this function. However, uptake of cysteine into neurons via EAAC1 contributes to neuronal antioxidant function by providing cysteine substrate for glutathione synthesis. Mice in which the EAAC1 gene has been deleted were seen to have enhanced susceptibility to neuronal oxidative stress and developed brain atrophy and cognitive function decline with aging. The aim of the current study was to evaluate if EAAC1 confers protection against ischemic events. Young adult CD-1 wild-type or EAAC1(-/-) mice were subjected to 30 min of bilateral common carotid artery occlusion and evaluated for neuronal death and zinc translocation. The intensity of TSQ fluorescence in the cytoplasm of cortical neurons in the EAAC1(-/-) mice was significantly higher than wild-type mice, indicating that the cortical neurons of EAAC1(-/-) mice contain higher cytoplasmic concentrations of labile (or free) zinc. Zinc translocation into cortical neurons was also enhan...Continue Reading

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Citations

Mar 7, 2013·Amino Acids·Koji Aoyama, Toshio Nakaki
Apr 1, 2014·Acta Pharmacologica Sinica·Weronika KrzyżanowskaJoanna Pera
Jan 15, 2014·Neurochemistry International·Stephanie M RobertHarald Sontheimer
Dec 6, 2019·Frontiers in Pharmacology·Angélica P EscobarPablo R Moya
Aug 14, 2020·International Journal of Molecular Sciences·Minwoo LeeSang Won Suh
Aug 8, 2021·International Journal of Molecular Sciences·Youichirou HigashiMotoaki Saito

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