Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment

Sironi, L.; Banfi, C.; Brioschi, M.; Gelosa, P.; Guerrini, U.; Nobili, E.; Gianella, A.; Paoletti, R.; Tremoli, E.; Cimino, M.

doi:10.1016/j.nbd.2005.12.004

We investigated the effects of simvastatin treatment on the expression of IL-1beta and MCP-1, the activity of NF-kB, and the signaling pathways related to NF-kB activation in a rat model of permanent middle cerebral artery occlusion (pMCAO). IL-1beta and MCPA expression, determined using RT-PCR, was enhanced by pMCAO; this effect was inhibited by the administration of simvastatin before ischemia. Pre-treatment with simvastatin abolished the ischemia-induced activation of NF-kB observed in vehicle-treated animals. The evaluation of signal transduction pathways, including extracellular signal-regulated kinase (ERK1/2), SAPK/JNK 46/54 and p38, indicated that only ERK1/2 phosphorylation was enhanced by ischemia, and this activation was prevented by simvastatin. ERK1/2-inhibitor, U0126, reduced brain ischemia but not cytokine induction. These results provide evidence that the HMG-CoA reductase inhibitor induces its effect in the protection of ischemic brain damage with a more complex mechanism which also involve anti-inflammatory properties rather than simple inhibition of ERK1/2 signaling pathway. (c) 2005 Elsevier Inc. All rights reserved.

Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment / L. SIRONI, C. BANFI, M. BRIOSCHI, P. GELOSA, U. GUERRINI, E. NOBILI, A. GIANELLA, R. PAOLETTI, E. TREMOLI, M. CIMINO. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 22:2(2006), pp. 445-451.

Titolo:	Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment
Autori:	SIRONI, LUIGI (Primo) BANFI, CRISTINA (Secondo) BRIOSCHI, MAURA GELOSA, PAOLO GUERRINI, ULIANO NOBILI, ELENA A. GIANELLA PAOLETTI, RODOLFO TREMOLI, ELENA (Penultimo) M. CIMINO mostra contributor esterni nascondi contributor esterni
Parole Chiave:	statin; inflammation; cerebral ischemia; permanent middle; cerebral artery occlusion; transcription factor; MAP kinase; rat
Settore Scientifico Disciplinare:	Settore BIO/14 - Farmacologia
Data di pubblicazione:	2006
Rivista:	NEUROBIOLOGY OF DISEASE
URL:	http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNK-4J7B0W4-5&_user=1080510&_coverDate=05%2F31%2F2006&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000051355&_version=1&_urlVersion=0&_userid=1080510&md5=504aa6848d0b3f2f989f78974c016a02
Tipologia:	Article (author)
Digital Object Identifier (DOI):	http://dx.doi.org/10.1016/j.nbd.2005.12.004
Appare nelle tipologie:	01 - Articolo su periodico

File in questo prodotto:

Non ci sono file associati a questo prodotto.

Pubblicazioni consigliate

Loading suggested articles...

Utilizza questo identificativo per citare o creare un link a questo documento:
http://hdl.handle.net/2434/24224

Citazioni

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

IRIS Institutional Research Information System - AIR Archivio Istituzionale della Ricerca

File in questo prodotto:

Pubblicazioni consigliate