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. PKCbetaII and PKCdelta isoforms were activated during aglycemic hypoxia. CGP53353, a specific PKCbetaII inhibitor, significantly attenuated aglycemic hypoxia-induced BBB hyperpermeability and disruption of occludin and zonula occludens-1 (ZO-1), indicating a deleterious role of PKCbetaII in the regulation of BBB permeability during aglycemic hypoxia. Conversely, rottlerin, a specific PKCdelta inhibitor, exacerbated BBB hyperpermeability and tight junction (TJ) disruption during aglycemic hypoxia, indicating a protective role of PKCdelta against aglycemic hypoxia-induced BBB hyperpermeability. Furthermore, disruption of TJ proteins during aglycemic hypoxia was attenuated by PKCbetaII DN and PKCdelta WT overexpression, and aggravated by PKCbetaII WT and PKCdelta DN overexpression. These results suggest that PKCbetaII and PKCdelta counter-regulate BBB permeability during aglycemic hypoxia.
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