Faculty Collaboration Database

p38 mitogen-activated protein kinase and calcium channels mediate signaling in depolarization-induced activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha in neurons. J Neurosci Res 2010 Feb 15;88(3):640-9

Date

09/24/2009

Pubmed ID

19774670

Pubmed Central ID

PMC3710696

DOI

10.1002/jnr.22222

Scopus ID

2-s2.0-73949119606 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) coactivates a number of transcription factors critical for mitochondrial biogenesis. Previously, we found that the expression of PGC-1alpha is governed by neuronal activity, but the signaling mechanism is poorly understood. The present study aimed at testing our hypothesis that depolarizing activation of PGC-1alpha in neurons is mediated by p38 mitogen-activated protein kinase (MAPK) and calcium channels. Cultured primary neurons and N2a cells were depolarized with 20 mM KCl for varying times, and increases in PGC-1alpha mRNA and protein levels were found after 0.5 and 1 hr of stimulation, respectively. These levels returned to those of controls after the withdrawal of KCl. Significantly, 15 min of KCl stimulation induced an up-regulation of both p38 MAPK and phosphorylated p38 MAPK that were suppressed by 30 min of pretreatment with SB203580, a blocker of p38 MAPK that also blocked the up-regulation of PGC-1alpha by KCl. Likewise, 30 min of pretreatment with nifedipine, a calcium channel blocker, also prevented the up-regulation of PGC-1alpha mRNA and proteins by KCl. Furthermore, a knockdown of p38 MAPK with small interference hairpin RNA significantly suppressed PGC-1alpha mRNA and protein levels. Our results indicate that both p38 MAPK and calcium play important roles in mediating signaling in depolarization-induced activation of PGC-1alpha at the protein and message levels in neurons.

Author List

Liang HL, Dhar SS, Wong-Riley MT

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

Animals
Calcium Channels
Cell Line, Tumor
Cells, Cultured
Membrane Potentials
Mice
Neurons
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Phosphorylation
Potassium Chloride
RNA, Messenger
RNA-Binding Proteins
Rats
Rats, Sprague-Dawley
Time Factors
Trans-Activators
Transcription Factors
Up-Regulation
Visual Cortex
p38 Mitogen-Activated Protein Kinases