Regulation of PGC-1alpha and PGC-1alpha-responsive genes with forskolin-induced Schwann cell differentiation.
Recent evidence indicates that mitochondrial homeostasis is critical for myelination and maintenance of peripheral nerve function. Mice lacking the metabolic transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) show reductions in expression of myelin-related proteins and exhibit myelin-associated lesions, so we identified PGC-1alpha target genes in Schwann cells (SCs) in vitro to determine potential roles for PGC-1alpha in glia and tested whether PGC-1alpha was sufficient for SC differentiation and myelination. Forskolin-induced differentiation was associated with an upregulation of PGC-1alpha mRNA and protein, and while overexpression of PGC-1alpha upregulated genes such as manganese superoxide dismutase and estrogen-related receptor alpha, it was not sufficient for induction of differentiation. Both PGC-1alpha overexpression and forskolin exposure caused an increase in the mitochondrial fusion-related protein mitofusin 1. These studies suggest that PGC-1alpha might be a potential target to promote mitochondrial stability during differentiation and myelination.
Cowell
Rita M
RM
Department of Psychiatry, University of Alabama, Birmingham, AL 35294, USA.
Blake
Kathryn R
KR
Inoue
Tatsuya
T
Russell
James W
JW
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects*; D012584:Sciatic Nerve / Q000166:cytology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000097983:ERRalpha Estrogen-Related Receptor
D005576:Colforsin; D049452:Green Fluorescent Proteins; D007211:Indoles; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C489709:Mfn1 protein, rat; C501429:Ppargc1a protein, rat; C007293:DAPI