title: Decreased cysteine uptake by EAAC1 gene deletion exacerbates neuronal oxidative stress and neuronal death after traumatic brain injury.
abstract: 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.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: In Yeol
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Kho
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Nursing, Inha University, Incheon, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Neurology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Song
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea. swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000111:Acetylcysteine / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D050580:Excitatory Amino Acid Transporter 3 / Q000172:deficiency*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493399:Slc1a1 protein, mouse; D000111:Acetylcysteine
keywords: Cysteine; EAAC1; Microglia; Reactive oxygen species; TBI; Zinc