Repression of adenosine triphosphate–binding cassette transporter ABCG2 by estrogen increases intracellular glutathione in brain endothelial cells following ischemic reperfusion injury

Jin A. Shin, Sae Im Jeong, Hye Won Kim, Gyeonghui Jang, Dong Ryeol Ryu, Young Ho Ahn, Ji Ha Choi, Youn Hee Choi, Eun Mi Park

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)138-148
Number of pages11
JournalNeurobiology of Aging
Volume66
DOIs
StatePublished - Jun 2018

Keywords

  • ABCG2
  • Brain endothelial cell
  • Estrogen
  • Glutathione
  • Ischemic stroke
  • Neuroprotection

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