The potentiation of ox-LDL induced apoptosis by inhibition of NF-kappa B

We previously reported that oxidized low density lipoprotein (ox-LDL) induc ed apoptosis in vascular smooth muscle cells (VSMCs). However, the transcri ption factors important for apoptotic signalling have been little clarified . We investigated the involvement of nuclear factor-kappa B (NF-kappa B), b y which apoptotic signalling is reported to be mediated, in ox-LDL-induced apoptosis. The effect of ox-LDL on the transcriptional factor NF-kappa B ac tivation was investigated by electrophoretic mobility shift assay (EMSA), O x-LDL caused NF-kappa B activation in VSMCs. Next, we investigated the effe ct on ox-LDL-induced apoptosis by introduction of synthetic double-stranded DNA with high affinity for NF kappa B in vitro as "decoy" cis elements tha t bind the transcriptional factor. Treatment by transfection of NF-kappa B decoy oligodeoxynucleotides (ODN), but not scramble ones, blunted the activ ation of NF-kappa B by ox-LDL and caused a significant further induction of ox-LDL-induced apoptosis. Results indicate that the activation of NF-kappa B prevents excessive apoptosis by ox-LDL in VSMCs. (C) 2000 Elsevier Scien ce Inc. All rights reserved.