Decreased nuclear factor-kappaB DNA binding activity following permanent focal cerebral ischaemia in the rat.
Many factors implicated in the pathogenesis of cerebral ischaemia such as glutamate, tumour necrosis factor and interleukin-1 have also been shown to activate nuclear factor-kappaB (NF-kappaB). In the present study we have investigated NF-kappaB activity at various times following permanent focal cerebral ischaemia in rats using immunohistochemistry, western blotting and electrophoretic mobility shift assay (EMSA). Three hours following middle cerebral artery occlusion nuclear translocation of NF-kappaB was detected using immunohistochemical and western blotting techniques. This was reflected in a trend towards increased NF-kappaB binding activity (EMSA) in the ischaemic cortex compared to histologically normal tissue. In contrast however, from 6 to 48 h post-occlusion nuclear translocation and NF-kappaB binding activity was decreased in the ischaemic cortex. Decreased NF-kappaB binding activity detected in degenerating neurones, suggests that decreased NF-kappaB activity may exacerbate ischaemia induced neuronal cell death.
Irving
E A
EA
Department of Neuroscience Research SmithKline Beecham Pharmaceuticals, Essex, Harlow, UK.
Hadingham
S J
SJ
Roberts
J
J
Gibbons
M
M
Chabot-Fletcher
M
M
Roshak
A
A
Parsons
A A
AA
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016328:NF-kappa B; D004247:DNA