SOD1 down-regulates NF-kappa B and c-mye expression in mice after transient focal cerebral ischemia

Citation
Cy. Huang et al., SOD1 down-regulates NF-kappa B and c-mye expression in mice after transient focal cerebral ischemia, J CEREBR B, 21(2), 2001, pp. 163-173
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
ISSN journal
0271-678X → ACNP
Volume
21
Issue
2
Year of publication
2001
Pages
163 - 173
Database
ISI
SICI code
0271-678X(200102)21:2<163:SDNBAC>2.0.ZU;2-F
Abstract
Reactive oxygen species (ROS) are implicated in reperfusion injury after fo cal cerebral ischemia (FCI). Reactive oxygen species regulate activity of t ranscription factors like NF-kappaB. The authors investigated the role of R OS in NF-kappaB activity after FCI using transgenic mice that overexpressed human coppcr/zinc-superoxide dismutase: (SODI) and that had reduced infarc tion volume after FCI. Superoxide dismutase transgenic and wild-type mice w ere subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subs equent reperfusion. Immunohistochemistry showed SODI overexpression attenua ted ischemia-induced NF-kappaB p65 immunoreactivity. Colocalization of NF-k appaB and the neuronal marker, microtubule-associated proteins (MAPs), show ed that NF-kappaB was up-regulated in neurons after FCI. Electrophoretic mo bility shift assays showed that SOD1 overexpression reduced ischemia-induce d NF-kappaB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF -kappaB downstream gene, was increased in the ischemic cortex and colocaliz ed with NF-KB. Western blotting showed that SOD1 overexpression reduced NF- KB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings pr ovide the first evidence that SOD 1 overexpression attenuates activation of NF-kappaB after transient FCI in mice and that preventing this early activ ation may block expression of downstream deleterious genes like c-myc, ther eby reducing ischemic damage.