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.
Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment
L. SIRONIPrimo
;C. BANFISecondo
;M. BRIOSCHI;P. GELOSA;U. GUERRINI;E. NOBILI;R. PAOLETTI;E. TREMOLIPenultimo
;
2006
Abstract
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.Pubblicazioni consigliate
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