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p38 mitogen‐activated protein kinase and calcium channels mediate signaling in depolarization‐induced activation of peroxisome proliferator‐activated receptor gamma coactivator‐1α in neurons
Author(s) -
Liang Huan Ling,
Dhar Shilpa S.,
WongRiley Margaret T.T.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22222
Subject(s) - coactivator , protein kinase a , p38 mitogen activated protein kinases , microbiology and biotechnology , depolarization , mapk/erk pathway , peroxisome proliferator activated receptor , voltage dependent calcium channel , biology , stimulation , gene knockdown , receptor , signal transduction , chemistry , kinase , calcium , endocrinology , transcription factor , biochemistry , apoptosis , gene , organic chemistry
Peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) coactivates a number of transcription factors critical for mitochondrial biogenesis. Previously, we found that the expression of PGC‐1α 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‐1α 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‐1α 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‐1α by KCl. Likewise, 30 min of pretreatment with nifedipine, a calcium channel blocker, also prevented the up‐regulation of PGC‐1α mRNA and proteins by KCl. Furthermore, a knockdown of p38 MAPK with small interference hairpin RNA significantly suppressed PGC‐1α 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‐1α at the protein and message levels in neurons. © 2009 Wiley‐Liss, Inc.