Activation of nuclear factor-kappaB in the rabbit spinal cord following ischemia and reperfusion.
The transcription factor NF-kappaB is a ubiquitously expressed inducible regulator of a broad range of genes. Recent studies have shown that activation of NF-kappaB predominantly is associated with protecting cells from apoptosis, but in some cell models, it is associated with promoting cell death. We used a rabbit spinal cord model of reversible ischemia to determine whether NF-kappaB was activated by ischemic and reperfusion injury. DNA binding activity of NF-kappaB was analyzed by an electrophoretic mobility shift assay in animals subjected to varying durations of ischemia and reperfusion. A low level of constitutive NF-kappaB DNA binding was detected in normal lumbar spinal cord extracts. Animals subjected to a short ischemic insult of 15 min, from which they usually recover neurologic function, had a significant increase in the amount of active NF-kappaB in nuclear extracts after 18 h reperfusion. There was no change in nuclear NF-kappaB DNA binding in animals occluded for 60 min that are permanently paraplegic and exhibit extensive neuropathological damage. The amount of deoxycholate-releasable NF-kappaB sequestered in the cytosol, however, decreased after 18 h reperfusion in rabbits occluded for 60 min. This correlated with a decrease in the amount of RelA(p65) NF-kappaB subunit. The results suggest that activation of NF-kappaB after a limited ischemic injury may participate in a neuroprotective response and not in cell death.
Zhang
S
S
Department of Neurosciences, University of California at San Diego, La Jolla, San Diego, CA 92093-0624, USA.
Tobaru
T
T
Zivin
J A
JA
Shackelford
D A
DA
D000818:Animals; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D017403:In Situ Hybridization; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010264:Paraplegia / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D013116:Spinal Cord / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism*
D015342:DNA Probes; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D004247:DNA