Faculty Collaboration Database

Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons. Biochim Biophys Acta 2009 Oct;1793(10):1604-13

Date

07/21/2009

Pubmed ID

19615412

Pubmed Central ID

PMC2744647

DOI

10.1016/j.bbamcr.2009.07.001

Scopus ID

2-s2.0-69949105097 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts down-regulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.

Author List

Dhar SS, Liang HL, Wong-Riley MT

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Binding Sites
Cell Line
Cells, Cultured
DNA Primers
Electron Transport Complex IV
Energy Metabolism
In Vitro Techniques
Mice
Models, Neurological
Mutagenesis, Site-Directed
Neurons
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nuclear Respiratory Factor 1
Promoter Regions, Genetic
Protein Interaction Domains and Motifs
RNA Interference
RNA, Messenger
Rats
Recombinant Proteins
Synaptic Transmission
Tetrodotoxin
Transcription, Genetic