Oxygen-Glucose Deprivation/Reoxygenation Induces Human Brain Microvascular Endothelial Cell Hyperpermeability Via VE-Cadherin Internalization: Roles of RhoA/ROCK2.

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Tytuł:: Oxygen-Glucose Deprivation/Reoxygenation Induces Human Brain Microvascular Endothelial Cell Hyperpermeability Via VE-Cadherin Internalization: Roles of RhoA/ROCK2.
Autorzy:: Chen J; Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Sun L; Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Ding GB; Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Chen L; Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiang L; Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Wang J; The Laboratory of Neurotoxicology, School of Public Health, Nanjing Medical University, Nanjing, China. .
Wu J; Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. .
Źródło:: Journal of molecular neuroscience : MN [J Mol Neurosci] 2019 Sep; Vol. 69 (1), pp. 49-59. Date of Electronic Publication: 2019 Jun 11.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Totowa, NJ : Humana Press
Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989-
MeSH Terms:: Cell Membrane Permeability*
Cadherins/*metabolism
Cell Membrane/*metabolism
Endothelial Cells/*metabolism
Glucose/*deficiency
Oxygen/*metabolism
Brain/blood supply ; Cell Hypoxia ; Cells, Cultured ; Endocytosis ; Endothelium, Vascular/cytology ; Humans ; Microvessels/cytology ; rho-Associated Kinases/metabolism ; rhoA GTP-Binding Protein/metabolism
References:: Invest Ophthalmol Vis Sci. 2001 Apr;42(5):941-7. (PMID: 11274070)
Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1485-94. (PMID: 11893586)
J Cell Biol. 2003 Nov 10;163(3):535-45. (PMID: 14610056)
Circ J. 2004 Jan;68(1):1-5. (PMID: 14695457)
Stroke. 2005 Oct;36(10):2251-7. (PMID: 16141422)
Ann N Y Acad Sci. 2008 Mar;1123:134-45. (PMID: 18375586)
Nat Cell Biol. 2008 Aug;10(8):923-34. (PMID: 18604199)
Nat Rev Mol Cell Biol. 2008 Sep;9(9):690-701. (PMID: 18719708)
Neurobiol Dis. 2010 Jun;38(3):376-85. (PMID: 20302940)
Curr Opin Cell Biol. 2010 Oct;22(5):651-8. (PMID: 20708398)
PLoS One. 2012;7(5):e37195. (PMID: 22606350)
Neurology. 2012 Sep 25;79(13 Suppl 1):S52-7. (PMID: 23008413)
J Physiol. 2013 Jan 15;591(2):461-73. (PMID: 23090948)
Mol Cell Biochem. 2014 Feb;387(1-2):39-53. (PMID: 24136461)
J Stroke Cerebrovasc Dis. 2014 Oct;23(9):2316-21. (PMID: 25156783)
Neuroimage Clin. 2014 Sep 10;6:262-74. (PMID: 25379439)
Cell Adh Migr. 2014;8(2):158-64. (PMID: 25422846)
Curr Opin Neurol. 2015 Dec;28(6):556-64. (PMID: 26402408)
Stroke. 2015 Nov;46(11):3310-5. (PMID: 26463696)
Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):119-24. (PMID: 26529544)
J Cell Sci. 2016 Jan 1;129(1):206-18. (PMID: 26598555)
PLoS One. 2016 Jan 15;11(1):e0146094. (PMID: 26771557)
Tissue Barriers. 2016 Feb 26;4(1):e1154641. (PMID: 27141427)
Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1243-E1252. (PMID: 28137866)
Fluids Barriers CNS. 2017 Mar 28;14(1):8. (PMID: 28351417)
Small GTPases. 2017 Sep 26;:1-19. (PMID: 28949796)
Curr Neuropharmacol. 2018;16(9):1375-1384. (PMID: 29473514)
Neuroscience. 2018 May 1;377:105-113. (PMID: 29522856)
Exp Cell Res. 2018 Aug 15;369(2):275-283. (PMID: 29842876)
Am J Physiol Cell Physiol. 2019 Feb 1;316(2):C252-C263. (PMID: 30462535)
Sci Rep. 2019 Feb 22;9(1):2567. (PMID: 30796241)
Grant Information:: 81701872 the National Natural Science Foundation of China (CN); 2015NJMUZD010 the Nanjing Medical University Science and Technology Development Fund Project
Contributed Indexing:: Keywords: HBMECs permeability; Oxygen-glucose deprivation and reoxygenation; RhoA/ROCK signaling pathway; VE-cadherin
Substance Nomenclature:: 0 (Cadherins)
124671-05-2 (RHOA protein, human)
EC 2.7.11.1 (ROCK2 protein, human)
EC 2.7.11.1 (rho-Associated Kinases)
EC 3.6.5.2 (rhoA GTP-Binding Protein)
IY9XDZ35W2 (Glucose)
S88TT14065 (Oxygen)
Entry Date(s):: Date Created: 20190613 Date Completed: 20200121 Latest Revision: 20200225
Update Code:: 20240104
DOI:: 10.1007/s12031-019-01326-8
PMID:: 31187440
: Czasopismo naukowe

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The destruction of the blood-brain barrier (BBB) contributes to a spectrum of neurological diseases such as stroke, and the hyperpermeability of endothelial cells is one of the characters of stroke, which is possibly exacerbated after reperfusion. However, the underlying mechanisms involving hyperpermeability after reperfusion between the endothelial cells remain poorly understood. Therefore, in the present study, the human microvascular endothelial cells (HBMECs) were exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic ischemic stroke condition in vitro with the aim to investigate the potential mechanisms induced by OGD/R. The permeability of cultured HBMECs was measured using FITC-labeled dextran in a Transwell system and transendothelial electrical resistance (TEER), while the RhoA activity was detected by pull-down assay. In addition, the phosphorylation of MYPT1, which reflects the activation of ROCK and the internalization of VE-cadherin, was detected by Western blot. It showed that OGD/R treatment significantly increased the permeability of HBMEC monolayers and facilitated the internalization of VE-cadherin in HBMEC monolayers. Pull-down assay showed that RhoA activation was obviously enhanced after OGD/R treatment, while RhoA and ROCK inhibitor significantly reversed OGD/R-induced HBMEC monolayers hyperpermeability and the internalization of VE-cadherin. Meanwhile, the knockdown assay showed that RhoA small interfering RNA (siRNA) led to similar effects. The inactivation of the downstream effector protein ROCK was also examined. Intriguingly, ROCK2 rather than ROCK1 exerted its adverse effects on HBMEC monolayer integrity, since ROCK2 knockdown markedly reverses the injury of OGD/R in HBMEC monolayers. In conclusion, the present study provides evidence that OGD/R may induce HBMEC monolayer hyperpermeability via RhoA/ROCK2-mediated VE-cadherin internalization, which may provide an impetus for the development of therapeutics targeting BBB damage in ischemic stroke.

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