Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons. J Neurochem 2009 Mar;108(6):1595-606
Date
01/27/2009Pubmed ID
19166514Pubmed Central ID
PMC3715120DOI
10.1111/j.1471-4159.2009.05929.xScopus ID
2-s2.0-61349104373 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
Neuronal activity, especially of the excitatory glutamatergic type, is highly dependent on energy from the oxidative pathway. We hypothesized that the coupling existed at the transcriptional level by having the same transcription factor to regulate a marker of energy metabolism, cytochrome c oxidase (COX) and an important subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors, GluR2 (Gria2). Nuclear respiratory factor 1 (NRF-1) was a viable candidate because it regulates all COX subunits and potentially activates Gria2. By means of in silico analysis, electrophoretic mobility shift and supershift, chromatin immunoprecipitation, and promoter mutational assays, we found that NRF-1 functionally bound to Gria2 promoter. Silencing of NRF-1 with small interference RNA prevented the depolarization-stimulated up-regulation of Gria2 and COX, and over-expression of NRF-1 rescued neurons from tetrodotoxin-induced down-regulation of Gria2 and COX transcripts. Thus, neuronal activity and energy metabolism are tightly coupled at the molecular level, and NRF-1 is a critical agent in this process.
Author List
Dhar SS, Liang HL, Wong-Riley MTMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Cells, Cultured
Chromatin Immunoprecipitation
Cyclooxygenase 2
Electron Transport Complex IV
Electrophoretic Mobility Shift Assay
Energy Metabolism
Isoquinolines
Mice
Mutagenesis
Neuroblastoma
Neurons
Nuclear Respiratory Factor 1
Potassium Chloride
Promoter Regions, Genetic
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Transfection
Visual Cortex
