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Brain Endothelial Cells Utilize Glycolysis for the Maintenance of the Transcellular Permeability

Authors
Kim, Eun SeonKim, Kyu-SungLee, Chan HeeJeon, Min-TaeLee, Sung BaeLee, Jong HwaKim, Do-Geun
Issue Date
Jul-2022
Publisher
Humana Press, Inc.
Keywords
BBB; Endothelial cells; Glucose; Energy metabolism; Transcytosis
Citation
Molecular Neurobiology, v.59, no.7, pp.4315 - 4333
Journal Title
Molecular Neurobiology
Volume
59
Number
7
Start Page
4315
End Page
4333
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/224
DOI
10.1007/s12035-022-02778-7
ISSN
0893-7648
Abstract
Among the components of the blood-brain barrier (BBB), endothelial cells (ECs) play an important role in supplying limited materials, especially glucose, to the brain. However, the mechanism by which glucose is metabolized in brain ECs is still elusive. To address this topic, we assessed the metabolic signature of glucose utilization using live-cell metabolic assays and liquid chromatography-tandem mass spectrometry metabolomic analysis. We found that brain ECs are highly dependent on aerobic glycolysis, generating lactate as its final product with minimal consumption of glucose. Glucose treatment decreased the oxygen consumption rate in a dose-dependent manner, indicating the Crabtree effect. Moreover, when glycolysis was inhibited, brain ECs showed impaired permeability to molecules utilizing transcellular pathway. In addition, we found that the blockade of glycolysis in mouse brain with 2-deoxyglucose administration resulted in decreased transcellular permeability of the BBB. In conclusion, utilizing glycolysis in brain ECs has critical roles in the maintenance and permeability of the BBB. Overall, we could conclude that brain ECs are highly glycolytic, and their energy can be used to maintain the transcellular permeability of the BBB.
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연구본부 (신경회로 연구그룹)
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