K+ regulates DNA binding of transcription factors to control gene expression related to neuronal apoptosis.
The loss of intracellular K+ promotes neuronal apoptosis. The mechanism by which K+ acts on apoptosis, however, remains largely unknown. Here we showed that K+ selectively affects DNA binding activity of transcriptional factors in vitro. Low K+ concentration ([K+]) promoted the DNA binding activity of p53 and Forkhead, proapoptotic transcriptional factors, whereas it inhibited that of cAMP-responsive element-binding protein, an anti-apoptotic transcriptional factor. In contrast, K+ did not affect the DNA binding activity of Ying Yang 1, CCAAT/enhancer binding protein and early growth response protein-1. The expression of bax and bim, proapoptotic genes known to be regulated by p53 and Forkhead, respectively, was enhanced in cortical neurons deprived of serum, a condition known to cause K+ loss, whereas the expression of c-fos, a cAMP-responsive element-binding protein target gene, was inhibited. Furthermore, blocking K+ channels suppressed the enhancement of bim mRNA level and the reduction of c-fos mRNA level induced by K+ loss, whereas it had no effect on the stimulation of Forkhead or cAMP-responsive element-binding protein induced by K+ loss. These results suggest that low intracellular [K+] selectively affects DNA binding activity of transcriptional factors to regulate gene expression related to neuronal apoptosis.
Yang
Qiaoyun
Q
Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, PR China.
Yan
Dong
D
Wang
Yizheng
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015345:Oligonucleotide Probes; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D014157:Transcription Factors; D004247:DNA; D011188:Potassium