PMID- 17870059 OWN - NLM STAT- MEDLINE DCOM- 20080125 LR - 20161124 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1175 DP - 2007 Oct 17 TI - Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons. PG - 10-6 AB - 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. FAU - Meng, Hui AU - Meng H AD - Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Liang, Huan Ling AU - Liang HL FAU - Wong-Riley, Margaret AU - Wong-Riley M LA - eng PT - Journal Article DEP - 20070809 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, rat) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 660YQ98I10 (Potassium Chloride) SB - IM MH - Action Potentials/*genetics MH - Active Transport, Cell Nucleus/genetics MH - Animals MH - Animals, Newborn MH - Cell Nucleus/metabolism/ultrastructure MH - Cells, Cultured MH - Cytoplasm/metabolism/ultrastructure MH - Gene Expression Regulation/genetics MH - Microscopy, Electron, Transmission MH - Microscopy, Immunoelectron MH - Neurons/*metabolism/ultrastructure MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - Potassium Chloride/pharmacology MH - RNA-Binding Proteins/genetics/*metabolism MH - Rats MH - Ribosomes/metabolism/ultrastructure MH - Transcription Factors/genetics/*metabolism MH - Transcriptional Activation/*genetics MH - Up-Regulation/drug effects/physiology MH - Visual Cortex/*metabolism/ultrastructure EDAT- 2007/09/18 09:00 MHDA- 2008/01/26 09:00 CRDT- 2007/09/18 09:00 PHST- 2007/04/12 00:00 [received] PHST- 2007/07/20 00:00 [revised] PHST- 2007/07/31 00:00 [accepted] PHST- 2007/09/18 09:00 [pubmed] PHST- 2008/01/26 09:00 [medline] PHST- 2007/09/18 09:00 [entrez] AID - S0006-8993(07)01813-6 [pii] AID - 10.1016/j.brainres.2007.07.063 [doi] PST - ppublish SO - Brain Res. 2007 Oct 17;1175:10-6. doi: 10.1016/j.brainres.2007.07.063. Epub 2007 Aug 9.