Wang, YZ (reprint author), Chinese Acad Sci, Inst Neurosci, SIBS, Lab Neural Signal Transduct,Grad Sch, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,email@example.com
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-L The expression of bax and bim, proapoptotic genes known to be regulated by pS3 and Forkhead, respectively, was enhanced in cortical neurons deprived of serum, condition known to cause K+ loss, whereas the expression of cfos, 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.