Subtype activation and interaction of protein kinase C and mitogen-activated protein kinase controlling receptor expression in cerebral arteries and microvessels after subarachnoid hemorrhage

Saema Ansar, Lars Edvinsson

57 Citationer (Scopus)

Abstract

BACKGROUND AND PURPOSE: The pathogenesis of cerebral ischemia associated with subarachnoid hemorrhage (SAH) still remains elusive. The aim of this study was to examine the involvement of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) subtypes in the pathophysiology of cerebral ischemia after SAH in cerebral arteries and microvessels and to examine temporal activation of the kinases. We hypothesize that treatment with a MAPK or PKC inhibitor will prevent the SAH-induced kinase activation in brain vessels.

METHODS: SAH was induced by injecting 250 microL blood into the prechiasmatic cistern in the rat. The activation of different MAPK and PKC isotypes in large circle of Willis cerebral arteries and intracerebral microvessels was examined at 0, 1, 3, 6, 12, 24, and 48 hours after SAH and after intrathecal treatment with PKC or MAPK inhibitor by use of Western blot.

RESULTS: Among the 8 investigated PKC isoforms, only PKC delta was activated at 1 hour and at 48 hours, whereas PKC alpha was activated at 48 hours after SAH. For the MAPKs, there was early phosphorylation at 1 hour of extracellular signal-regulated kinase 1/2, whereas c-jun N-terminal kinase and p38 showed enhanced phosphorylation only at 48 hours after SAH. The pattern was identical in large cerebral arteries and in intracerebral microvessels. Treatment with either the PKC (RO-31-7549) or the raf (SB386023-b) inhibitor prevented the kinase activation.

CONCLUSIONS: The results show that specific subtypes of the MAPK and PKC pathways are activated in cerebral arteries after SAH and the PKC and raf inhibitors are able to prevent this activation.

OriginalsprogEngelsk
TidsskriftStroke; a journal of cerebral circulation
Vol/bind39
Udgave nummer1
Sider (fra-til)185-90
Antal sider6
ISSN0039-2499
DOI
StatusUdgivet - jan. 2008

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