Role of PKCβII and PKCδ in blood-brain barrier permeability during aglycemic hypoxia

被引：27

作者：

Kim, Young-Ae ^{[1
,2
]}

Park, Sung Lyea ^{[1
,2
]}

Kim, Mi-Young ^{[1
,2
]}

Lee, Soo Hwan ^{[1
]}

Baik, Eun Joo ^{[1
]}

Moon, Chang-Hyun ^{[1
]}

Jung, Yi-Sook ^{[1
,2
]}

机构：

[1] Ajou Univ, Sch Med, Dept Physiol, Suwon 443749, South Korea

[2] Ajou Univ, Brain Korea Mol Sci & Technol 21, Suwon 443749, South Korea

来源：

NEUROSCIENCE LETTERS | 2010年 / 468卷 / 03期

关键词：

Protein kinase C; Aglycemic hypoxia; Blood-brain barrier; Permeability; Tight junction; PROTEIN-KINASE-C; TIGHT JUNCTION PROTEINS; ENDOTHELIAL-CELLS; IN-VITRO; ACTIVATION; EXPRESSION; HYPOXIA/AGLYCEMIA; REPERFUSION; DYSFUNCTION; ISCHEMIA;

D O I：

10.1016/j.neulet.2009.11.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Blood-brain barrier (BBB) dysfunction contributes to the pathophysiology of cerebrovascular diseases such as stroke. In the present study, we investigated the role of PKC isoforms in aglycemic hypoxia-induced hyperpermeability, using an in vitro model of the BBB consisting of mouse bEnd.3 cells. PKC beta II and PKC delta isoforms were activated during aglycemic hypoxia. CGP53353, a specific PKC beta II inhibitor, significantly attenuated aglycemic hypoxia-induced BBB hyperpermeability and disruption of occludin and zonula occludens-1 (ZO-1), indicating a deleterious role of PKC beta II in the regulation of BBB permeability during aglycemic hypoxia. Conversely, rottlerin, a specific PKC delta inhibitor, exacerbated BBB hyperpermeability and tight junction (TJ) disruption during aglycemic hypoxia, indicating a protective role of PKC delta against aglycemic hypoxia-induced BBB hyperpermeability. Furthermore, disruption of TJ proteins during aglycemic hypoxia was attenuated by PKC beta II DN and PKC delta WT overexpression, and aggravated by PKC beta II WT and PKC delta DN overexpression. These results suggest that PKC beta II and PKC delta counter-regulate BBB permeability during aglycemic hypoxia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：254 / 258

页数：5

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