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AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke

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Author(s)
서지혜
Alternative Author(s)
Seo, Ji Hye
Issued Date
2020
Keyword
A-kinase anchor protein 12Rho kinasestrokeendothelial cellblood-brain barrier
Abstract
A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that associates with intracellular molecules to regulate multiple signal transductions. Although the roles of AKAP12 in the central nervous system are still relatively understudied, it was previously shown that AKAP12 regulates blood-retinal barrier formation. In this study, we asked whether AKAP12 also supports the function and integrity of the blood-brain barrier (BBB). In a mouse model of focal ischemia, the expression level of AKAP12 in cerebral endothelial cells was upregulated during the acute phase of stroke. Also, in cultured cerebral endothelial cells, oxygen-glucose deprivation induced the upregulation of AKAP12. When AKAP12 expression was suppressed by an siRNA approach in cultured endothelial cells, endothelial permeability was increased along with the dysregulation of ZO-1/Claudin 5 expression. In addition, the loss of AKAP12 expression caused an upregulation/activation of the Rho kinase pathway, and treatment of Rho kinase inhibitor Y-27632 mitigated the increase of endothelial permeability in AKAP12-deficient endothelial cell cultures. These in vitro findings were confirmed by our in vivo experiments using Akap12 knockout mice. Compared to wild-type mice, Akap12 knockout mice showed a larger extent of BBB damage after stroke. However, the inhibition of rho kinase by Y-27632 tightened the BBB in Akap12 knockout mice. These data may suggest that endogenous AKAP12 works to alleviate the damage and dysfunction of the BBB caused by ischemic stress. Therefore, the AKAP12-rho-kinase signaling pathway represents a novel therapeutic target for stroke.
Department
Dept. of Biochemistry (생화학)
Publisher
School of Medicine (의과대학)
Citation
Ji Hae Seo. (2020). AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke. International Journal of Molecular Sciences, 21(23), 9078-. doi: 10.3390/ijms21239078
Type
Article
ISSN
1422-0067
DOI
10.3390/ijms21239078
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/43448
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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