Low K⁺ Promotes NF-κB/DNA Binding in Neuronal Apoptosis Induced by K⁺ Loss

Abstract

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-κB 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-κB/DNA binding through direct effects on the interaction of NF-κB dimers with DNA. Up-regulation of proapoptotic protein Bcl-X_S and neuronal apoptosis induced by serum deprivation are blocked by inhibition and/or down-regulation of NF-κB and by prevention of K⁺ loss. Thus, a direct action of K⁺ on NF-κB/DNA binding regulates gene transcription related to neuronal apoptosis.

We thank A. Lin for kindly providing κB-luciferase and p50 plasmids, T. Tsukahara for pGL2 (848) and pGLκBM plasmids, D. Baltimore for ChIP assay protocol, M-m. Poo and L. Mei for helpful suggestions and critical comments, Q. Hu for technical assistance on confocal imaging, Y.-c. Jia for siRNA experiments, and Z.-j. Fan for cortical cell preparations.

This work was supported by grants from the Major State Basic Research Program of China (G200077800) and projects 30321002 and 30225025 from the National Natural Science Foundation of China.