RGD Reference Report - IkappaB-alpha expression following transient focal cerebral ischemia is modulated by nitric oxide. - Rat Genome Database
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IkappaB-alpha expression following transient focal cerebral ischemia is modulated by nitric oxide.

Authors: Greco, R  Mangione, AS  Amantea, D  Bagetta, G  Nappi, G  Tassorelli, C 
Citation: Greco R, etal., Brain Res. 2011 Feb 4;1372:145-51. doi: 10.1016/j.brainres.2010.11.071. Epub 2010 Nov 28.
RGD ID: 10413868
Pubmed: (View Article at PubMed) PMID:21122797
DOI: Full-text: DOI:10.1016/j.brainres.2010.11.071

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-kappaB 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-kappaB activation. IkB-alpha expression decreased in ischemic cortices when compared with the cortices of the sham group, thus confirming the activation of NF-kappaB 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-kappaB activation via IkB-alpha modulation and mediates ischemic-related damage in the brain following ischemia.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Nfkbia  (NFKB inhibitor alpha)

Genes (Mus musculus)
Nfkbia  (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha)

Genes (Homo sapiens)
NFKBIA  (NFKB inhibitor alpha)


Additional Information