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Repression of adenosine triphosphate-binding cassette transporter ABCG2 by estrogen increases intracellular glutathione in brain endothelial cells following ischemic reperfusion injury
- Title
- Repression of adenosine triphosphate-binding cassette transporter ABCG2 by estrogen increases intracellular glutathione in brain endothelial cells following ischemic reperfusion injury
- Authors
- Shin, Jin A.; Jeong, Sae Im; Kim, Hye Won; Jang, Gyeonghui; Ryu, Dong-Ryeol; Ahn, Young-Ho; Choi, Ji Ha; Choi, Youn-Hee; Park, Eun-Mi
- Ewha Authors
- 박은미; 류동열; 최윤희; 최지하; 안영호
- SCOPUS Author ID
- 박은미; 류동열; 최윤희; 최지하; 안영호
- Issue Date
- 2018
- Journal Title
- NEUROBIOLOGY OF AGING
- ISSN
- 0197-4580
1558-1497
- Citation
- NEUROBIOLOGY OF AGING vol. 66, pp. 138 - 148
- Keywords
- ABCG2; Brain endothelial cell; Estrogen; Glutathione; Ischemic stroke; Neuroprotection
- Publisher
- ELSEVIER SCIENCE INC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- The adenosine triphosphate-binding cassette efflux transporter ABCG2, which is located in the blood-brain barrier limits the entry of endogenous compounds and xenobiotics into the brain, and its expression and activity are regulated by estrogen. This study was aimed to define the role of ABCG2 in estrogen-mediated neuroprotection against ischemic injury. ABCG2 protein levels before and after ischemic stroke were increased in the brain of female mice by ovariectomy, which were reversed by estrogen replacement. In brain endothelial cell line bEnd. 3, estrogen reduced the basal ABCG2 protein level and efflux activity and protected cells from ischemic injury without inducing ABCG2 expression. When bEnd. 3 cells were transfected with ABCG2 small interfering RNA, ischemia-induced cell death was reduced, and the intracellular concentration of glutathione, an antioxidant that is transported by ABCG2, was increased. In addition, after ischemic stroke in ovariectomized mice, estrogen prevented the reduction of intracellular glutathione level in brain microvessels. These data suggested that the suppression of ABCG2 by estrogen is involved in neuroprotection against ischemic injury by increasing intracellular glutathione, and that the modulation of ABCG2 activity offers a therapeutic target for brain diseases in estrogen-deficient aged women. (C) 2018 Elsevier Inc. All rights reserved.
- DOI
- 10.1016/j.neurobiolaging.2018.02.020
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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