Low K+ promotes NF-kappaB/DNA binding in neuronal apoptosis induced by K+ loss.
Low intracellular K+ concentration ([K+]i) promotes apoptosis and blocking K+ loss prevents apoptosis, but the mechanism of action of low [K+]i remains unclear. Here, we show that low [K+]i increases NF-kappaB transcriptional activity by enhancing its binding to the promoter of target genes without affecting its activation and nuclear translocation in cortical neurons deprived of serum. Low K+ concentration promotes NF-kappaB/DNA binding through direct effects on the interaction of NF-kappaB dimers with DNA. Up-regulation of proapoptotic protein Bcl-XS and neuronal apoptosis induced by serum deprivation are blocked by inhibition and/or down-regulation of NF-kappaB and by prevention of K+ loss. Thus, a direct action of K+ on NF-kappaB/DNA binding regulates gene transcription related to neuronal apoptosis.
Tao
Yanmei
Y
Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, People's Republic of China.
Yan
Dong
D
Yang
Qiaoyun
Q
Zeng
Rui
R
Wang
Yizheng
Y
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics*
C494813:Bcl2l1 protein, rat; D016328:NF-kappa B; D051020:bcl-X Protein; D004247:DNA; D011188:Potassium