K+ regulates DNA binding of transcription factors to control gene expression related to neuronal apoptosis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yang, Q; Yan, D; Wang, Y

Published Date

  • July 31, 2006

Published In

Volume / Issue

  • 17 / 11

Start / End Page

  • 1199 - 1204

PubMed ID

  • 16837854

Pubmed Central ID

  • 16837854

International Standard Serial Number (ISSN)

  • 0959-4965

Digital Object Identifier (DOI)

  • 10.1097/01.wnr.0000224

Language

  • eng

Conference Location

  • England