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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
Author(s) -
Dhar Shilpa S.,
Liang Huan Ling,
WongRiley Margaret T. T.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05929.x
Subject(s) - biology , ampa receptor , glutamatergic , transcription factor , chromatin immunoprecipitation , glutamate receptor , microbiology and biotechnology , biochemistry , receptor , promoter , gene expression , gene
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.