The potentiation of ox-LDL induced apoptosis by inhibition of NF-kappaB.
We previously reported that oxidized low density lipoprotein (ox-LDL) induced apoptosis in vascular smooth muscle cells (VSMCs). However, the transcription factors important for apoptotic signalling have been little clarified. We investigated the involvement of nuclear factor-kappaB (NF-kappaB), by which apoptotic signalling is reported to be mediated, in ox-LDL-induced apoptosis. The effect of ox-LDL on the transcriptional factor NF-kappaB activation was investigated by electrophoretic mobility shift assay (EMSA). Ox-LDL caused NF-kappaB activation in VSMCs. Next, we investigated the effect on ox-LDL-induced apoptosis by introduction of synthetic double-stranded DNA with high affinity for NF-kappaB in vitro as "decoy" cis elements that bind the transcriptional factor. Treatment by transfection of NF-kappaB decoy oligodeoxynucleotides (ODN), but not scramble ones, blunted the activation of NF-kappaB by ox-LDL and caused a significant further induction of ox-LDL-induced apoptosis. Results indicate that the activation of NF-kappaB prevents excessive apoptosis by ox-LDL in VSMCs.
Nishio
E
E
Department of Pharrmacology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Kanda
Y
Y
Kuroki
Y
Y
Watanabe
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D018716:Molecular Mimicry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity; D014162:Transfection
D008077:Lipoproteins, LDL; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D010710:Phosphates; C099252:oxidized low density lipoprotein; C083120:phosphorodithioic acid; D004247:DNA