T3-mediated gene expression is independent of PGC-1alpha.
Thyroid hormone (T3) has a profound influence on normal development, differentiation and metabolism, processes which are known to be regulated by the transcriptional coactivator PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha). Since T3 rapidly induces PGC-1alpha expression, we investigated whether reduced PGC-1alpha levels lead to alterations in T3-mediated gene expression patterns. Using RNA interference, we reduced PGC-1alpha mRNA to approximately 10% of its initial concentration in rat pituitary GC cells. Knock-down of PGC-1alpha is accompanied by diminished protein concentration and decreased expression level of PGC-1alpha target genes, among them key enzymes involved in gluconeogenesis, mitochondrial biogenesis and fatty acid oxidation. PGC-1alpha, PGC-1beta and NRF-1 mRNA molecules were rapidly degraded with a half-life time of approximately 90min, but this was independent of T3 stimulation. Expression of T3-target genes was not changed upon knock-down of PGC-1alpha. Our data indicate that complex T3-mediated gene expression patterns are maintained independently of PGC-1alpha activation.
Wulf
Anne
A
Institut für Biochemie und Molekularbiologie I, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
Harneit
Angelika
A
Weitzel
Joachim M
JM
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014284:Triiodothyronine