ETB receptor-mediated MMP-9 activation induces vasogenic edema via ZO-1 protein degradation following status epilepticus. (24th September 2015)

• Record Type: Journal Article
• Authors: Kim, J.Y.; Ko, A.-R.; Hyun, H.-W.; Kang, T.-C.
• Is Part Of: Neuroscience. Volume 304(2015)
• Page Start: 355
• Page End: 367
• Publication Date: 2015-09-24
• Subjects: BBB blood–brain barrier -- DAB 3, 3′-diaminobenzidine -- DTT dithiothreitol -- eNOS endothelial nitric oxide synthase -- ETB receptor endothelin B receptor -- GFAP glial fibrillary acidic protein -- MMP-9 matrix metalloproteinase-9 -- PB phosphate buffer -- PBS phosphate-buffered saline -- PC piriform cortex -- SD Sprague-Dawley -- SE status epilepsy -- TBS Tris-buffered saline -- TJ tight junction -- ZO zonula occludens; status epilepticus -- vasogenic edema -- claudin-5 -- occludin -- zonula occludens-1 -- eNOS; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.07.065
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: SE changed the expressions and subcellular localizations of TJ proteins. The alteration in zonula occludens-1 expression was relevant to vasogenic edema. ETB receptor-mediated eNOS activation increased MMP-9 activity. ETB receptor antagonism prevented ZO-1 degradation by inhibiting MMP-9 activation. ZO-1 degradation may be involved in vasogenic edema formation following SE. Abstract: The blood–brain barrier (BBB) is formed by the endothelial cells with specialized tight junctions (TJs) lining the blood vessels and astroglial endfeet surrounding the blood vessels. Although BBB disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process, little is known about the molecular and physiological events concerning vasogenic edema formation. In the present study, status epilepticus (SE) changed the expressions and subcellular localizations of TJ proteins (claudin-5, occludin and zonula occludens-1 (ZO-1)) in endothelial cells of the rat piriform cortex. Among TJ proteins, the alteration in ZO-1 expression was relevant to endothelin B (ETB ) receptor-mediated endothelial nitric oxide synthase (eNOS) activation, which increased matrix metalloproteinase-9 (MMP-9) activity. Indeed, BQ788 (an ETB receptor antagonist) effectively attenuated SE-induced vasogenic edema by inhibiting eNOS-mediated MMP-9 activation and ZO-1 protein degradation in endothelial cells, although astroglial endfeet were detached from endothelial cells. Therefore, we suggest that SE-induced ETB receptor/eNOS-mediated MMP-9 activation may lead to impairments of endothelial cell function via TJ protein degradation, which are involved in vasogenic edema formation independent of perivascular astroglial functions.