IkappaB-alpha expression following transient focal cerebral ischemia is modulated by nitric oxide - PubMed (original) (raw)
IkappaB-alpha expression following transient focal cerebral ischemia is modulated by nitric oxide
Rosaria Greco et al. Brain Res. 2011.
Abstract
The role of nitric oxide (NO) in cerebral ischemia/reperfusion (IR) has been intensively investigated. In general NO is regarded as a mediator of ischemia-associated neuronal damage, as inhibitors of NO synthesis ameliorate neuronal injury during permanent focal cerebral ischemia, however the exact role of NO in ischemia remains controversial. It has been previously shown that NO-donors can directly inhibit the DNA binding activity of NF-kappaB family proteins and strong evidence supports that activation of NF-κB contributes to ischemia-induced neuronal injury. In this study, we have investigated whether NO production by nNOS, eNOS and iNOS modulates IkB-alpha expression in cerebral ischemia, by using various inhibitors of NOS, in rats subjected to transient (1h) middle cerebral artery occlusion (tMCAo). Male Wistar rats were treated intraperitoneally (i.p.) with 3mg/kg of NG-nitro-l-arginine methyl ester (l-NAME, a non-selective NOS inhibitor), 5mg/kg of l-N6-(1-iminoethyl)-lysine (l-NIL, an inducible NOS inhibitor), 25mg/kg of 7-Nitroindazole (7-NI, a neuronal NOS inhibitor) and 10mg/Kg of l-N-(1-iminoethyl)ornithine (l-NIO, a selective eNOS inhibitor) 15min before the induction of tMCAo. Cortical IkB-alpha expression was evaluated by western blotting and its decrease was considered as an indicator of NF-κB activation. IkB-alpha expression decreased in ischemic cortices when compared with the cortices of the sham group, thus confirming the activation of NF-κB in ischemic conditions. Pre-treatment with l-NAME, l-NIL and 7-NI significantly reduced the infarct volume and prevented ischemia-induced reduction in IkB-alpha expression. Conversely, pretreatment with l-NIO was associated with a significant increase in infarct volume and a reduction in IkB-alpha expression. These findings suggest that NO of neuronal and inducible origin promotes NF-κB activation via IkB-alpha modulation and mediates ischemic-related damage in the brain following ischemia.
Copyright © 2010 Elsevier B.V. All rights reserved.
Similar articles
- Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury.
Shen J, Ma S, Chan P, Lee W, Fung PC, Cheung RT, Tong Y, Liu KJ. Shen J, et al. J Neurochem. 2006 Feb;96(4):1078-89. doi: 10.1111/j.1471-4159.2005.03589.x. Epub 2006 Jan 17. J Neurochem. 2006. PMID: 16417587 - Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats.
Tsai SK, Hung LM, Fu YT, Cheng H, Nien MW, Liu HY, Zhang FB, Huang SS. Tsai SK, et al. J Vasc Surg. 2007 Aug;46(2):346-53. doi: 10.1016/j.jvs.2007.04.044. Epub 2007 Jun 27. J Vasc Surg. 2007. PMID: 17600658 - Modulation of cerebral RAGE expression following nitric oxide synthase inhibition in rats subjected to focal cerebral ischemia.
Greco R, Demartini C, Zanaboni AM, Blandini F, Amantea D, Tassorelli C. Greco R, et al. Eur J Pharmacol. 2017 Apr 5;800:16-22. doi: 10.1016/j.ejphar.2017.02.008. Epub 2017 Feb 8. Eur J Pharmacol. 2017. PMID: 28188764 - Nitric oxide synthase in models of focal ischemia.
Samdani AF, Dawson TM, Dawson VL. Samdani AF, et al. Stroke. 1997 Jun;28(6):1283-8. doi: 10.1161/01.str.28.6.1283. Stroke. 1997. PMID: 9183363 Review. - [Lack of evidence that inducible nitric oxide synthase participates in the development of ischemic brain damage].
Nagafuji T, Suzuki M, Hosoi Y. Nagafuji T, et al. Nihon Yakurigaku Zasshi. 1998 Jan;111(1):45-53. doi: 10.1254/fpj.111.45. Nihon Yakurigaku Zasshi. 1998. PMID: 9551472 Review. Japanese.
Cited by
- Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells.
Quintana-Lopez L, Blandino-Rosano M, Perez-Arana G, Cebada-Aleu A, Lechuga-Sancho A, Aguilar-Diosdado M, Segundo C. Quintana-Lopez L, et al. Mediators Inflamm. 2013;2013:905175. doi: 10.1155/2013/905175. Epub 2013 Jun 12. Mediators Inflamm. 2013. PMID: 23840099 Free PMC article. - Rational modulation of the innate immune system for neuroprotection in ischemic stroke.
Amantea D, Micieli G, Tassorelli C, Cuartero MI, Ballesteros I, Certo M, Moro MA, Lizasoain I, Bagetta G. Amantea D, et al. Front Neurosci. 2015 Apr 29;9:147. doi: 10.3389/fnins.2015.00147. eCollection 2015. Front Neurosci. 2015. PMID: 25972779 Free PMC article. Review. - Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.
Cox-Limpens KE, Vles JS, LA van den Hove D, Zimmermann LJ, Gavilanes AW. Cox-Limpens KE, et al. BMC Neurosci. 2014 May 29;15:67. doi: 10.1186/1471-2202-15-67. BMC Neurosci. 2014. PMID: 24885038 Free PMC article. - Characterization of the Involvement of Tumour Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6) in Ischemic Brain Injury Caused by Middle Cerebral Artery Occlusion in Mouse.
Di Santo C, La Russa D, Greco R, Persico A, Zanaboni AM, Bagetta G, Amantea D. Di Santo C, et al. Int J Mol Sci. 2023 Mar 18;24(6):5800. doi: 10.3390/ijms24065800. Int J Mol Sci. 2023. PMID: 36982872 Free PMC article. - Preconditioning with a novel metallopharmaceutical NO donor in anesthetized rats subjected to brain ischemia/reperfusion.
Campelo MW, Oriá RB, Lopes LG, Brito GA, Santos AA, Vasconcelos RC, Silva FO, Nobrega BN, Bento-Silva MT, Vasconcelos PR. Campelo MW, et al. Neurochem Res. 2012 Apr;37(4):749-58. doi: 10.1007/s11064-011-0669-x. Epub 2011 Dec 10. Neurochem Res. 2012. PMID: 22160748
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources