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PBN inhibits a detrimental effect of methamphetamine on brain endothelial cells by alleviating the generation of reactive oxygen species

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Author(s)
Jong Su HwangEun Hye ChaByoungduck ParkEunyoung HaJi Hae Seo
Keimyung Author(s)
Ha, Eun YoungSeo, Ji Hye
Department
Dept. of Biochemistry (생화학)
Journal Title
Archive of Pharmacal Research
Issued Date
2020
Volume
43
Keyword
Blood–brain barrierMethamphetamineN-tert-butyl-α-phenylnitroneReactive oxygen species
Abstract
Methamphetamine (METH) is a powerful psychostimulant that is causing serious health problems worldwide owing to imprudent abuses. Recent studies have suggested that METH has deleterious effects on the blood–brain barrier (BBB). A few studies have also been conducted on the mechanisms whereby METH-induced oxidative stress causes BBB dysfunction. We investigated whether N-tert-butyl-α-phenylnitrone (PBN) has protective effects on BBB function against METH exposure in primary human brain microvascular endothelial cells (HBMECs). We found that METH significantly increased reactive oxygen species (ROS) generation in HBMECs. Pretreatment with PBN decreased METH-induced ROS production. With regard to BBB functional integrity, METH exposure elevated the paracellular permeability and reduced the monolayer integrity; PBN treatment reversed these effects. An analysis of the BBB structural properties, by immunostaining junction proteins and cytoskeleton in HBMECs, indicated that METH treatment changed the cellular localization of the tight (ZO-1) and adherens junctions (VE-cadherin) from the membrane to cytoplasm. Furthermore, METH induced cytoskeletal reorganization via the formation of robust stress fibers. METH-induced junctional protein redistribution and cytoskeletal reorganization were attenuated by PBN treatment. Our results suggest that PBN can act as a therapeutic reagent for METH-induced BBB dysfunction by inhibiting excess ROS generation.
Keimyung Author(s)(Kor)
하은영
서지혜
Publisher
School of Medicine (의과대학)
Citation
Jong Su Hwang et al. (2020). PBN inhibits a detrimental effect of methamphetamine on brain endothelial cells by alleviating the generation of reactive oxygen species. Archive of Pharmacal Research, 43, 1347–1355. doi: 10.1007/s12272-020-01284-5
Type
Article
ISSN
1976-3786
Source
https://link.springer.com/article/10.1007/s12272-020-01284-5#article-info
DOI
10.1007/s12272-020-01284-5
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43427
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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