title: EAAC1 gene deletion increases neuronal death and blood brain barrier disruption after transient cerebral ischemia in female mice.
abstract: EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1-/- female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood-brain barrier (BBB) disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1-/- female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. bychoi@hallym.ac.kr.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. fate0710@hallym.ac.kr.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. missgabong@hallym.ac.kr.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. supsock1126@naver.com.
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. inyeol@hallym.ac.kr.
authors.forename: In Yeol
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Nursing, Inha University, Incheon 402-751, Korea. sohnmin@inha.ac.kr.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea. swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005978:Glutathione / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine