Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons. Brain Res 2007 Oct 17;1175:10-6
Date
09/18/2007Pubmed ID
17870059DOI
10.1016/j.brainres.2007.07.063Scopus ID
2-s2.0-34848818263 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC- 1alpha) is a coactivator of nuclear receptors and other transcription factors that regulate several metabolic processes, including mitochondrial biogenesis, energy homeostasis, respiration, and gluconeogenesis. PGC-1alpha plays a vital role in stimulating genes that are important to oxidative metabolism and other mitochondrial functions in brown adipose tissue and skeleton muscles, but the significance of PGC-1alpha in the brain remains elusive. The goal of our present study was to determine by means of quantitative immuno-electron microscopy the expression of PGC-1alpha in cultured rat visual cortical neurons under normal conditions as well as after depolarizing stimulation for varying periods of time. Our results showed that: (a) PGC-1alpha was normally located in both the nucleus and the cytoplasm. In the nucleus, PGC-1alpha was associated mainly with euchromatin rather than heterochromatin, consistent with active involvement in transcription. In the cytoplasm, it was associated mainly with free ribosomes. (b) Neuronal depolarization by KCl for 0.5 h induced a significant increase in PGC-1alpha labeling density in both the nucleus and the cytoplasm (P<0.01). The heightened expression continued after 1 and 3 h of depolarizing treatment (P<0.01), but decreased from 5 h onward and returned to baseline level by 10 h. These results indicate that PGC-1alpha responds very early to increased neuronal activity by synthesizing more proteins in the cytoplasm and translocating them to the nucleus for gene activation. PGC-1alpha level in neurons is, therefore, tightly regulated by neuronal activity.
Author List
Meng H, Liang HL, Wong-Riley MMESH terms used to index this publication - Major topics in bold
Action PotentialsActive Transport, Cell Nucleus
Animals
Animals, Newborn
Cell Nucleus
Cells, Cultured
Cytoplasm
Gene Expression Regulation
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Neurons
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Potassium Chloride
RNA-Binding Proteins
Rats
Ribosomes
Transcription Factors
Transcriptional Activation
Up-Regulation
Visual Cortex
