Selective up-regulation of I kappaB-alpha in ischemic penumbra following focal cerebral ischemia.
Activation of transcription factor NF-kappaB plays a critical role in immune, inflammatory and cell death responses. In resting cells, NF-kappaB is sequestrated in the cytoplasm in an inactive form through its association with inhibitory proteins, I kappaB (e.g.I kappaB-alpha). In response to cell activation, I kappaB is degraded causing release of active NF-kappaB. Active NF-kappaB translocates into the nucleus leading to activation of transcription that may have a profound effect on cell survival, including that after ischemic stroke. Here, using Western blot analysis, we show that immunoreactivity to the major subunit of NF-kappaB, p65, as well as to the inhibitory subunit I kappaB-alpha is equally markedly decreased in the ischemic core after transient middle cerebral and common carotid artery occlusion in rats. In contrast, penumbral regions display no change in p65, and significant increase in I kappaB-alpha immunoreactivity, as compared to non-ischemic areas. In these penumbral regions with elevated I kappaB-alpha immunoreactivity, we find reduced cytosolic and increased nuclear I kappaB-alpha staining of neurons, as determined by immunohistochemistry. Altogether, these results suggest that an altered ratio between activating and inhibitory NF-kappaB pathways mediated through I kappaB-alpha may play an important role in survival of the ischemic penumbra.
Aronowski
J
J
Department of Neurology, University of Texas, Houston Medical School, 77030, USA.
Strong
R
R
Kang
H S
HS
Grotta
J C
JC
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D020672:I-kappa B Proteins; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D016900:Neurofilament Proteins; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha