Thyroid hormone increases transcription of GA-binding protein/nuclear respiratory factor-2 alpha-subunit in rat liver.
Thyroid hormone (TH) regulates mitochondrial respiratory rate by activating coordinated transcription in the nucleus and mitochondria. Whereas TH activates transcription of mitochondrial genes directly, the activation of nuclear-encoded mitochondrial genes is probably executed by indirect unknown mechanisms. Nuclear respiratory factors (NRF)-1 and GA-binding protein (BP)/NRF-2 may function as transacting genes, but regulation of these genes by TH is not demonstrated. We show that TH administration to hypothyroid rats promptly increases GABP/NRF-2 alpha-subunit mRNA levels in the liver, without significant changes in beta, gamma subunits. In run-on and time-course experiments, the transcription rate and protein levels increased three-fold in response to TH, indicating GABP/NRF-2 transcriptional regulation. The results also support the notion that ATP synthase beta-subunit is regulated by TH through the indirect activation of GABP/NRF-2.
Rodríguez-Peña
Angeles
A
Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain.
Escrivá
Héctor
H
Handler
Ana C
AC
Vallejo
Carmen G
CG
D025181:ATP Synthetase Complexes / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004334:Drug Administration Schedule; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000008:administration & dosage*
D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; C495649:Gabpa protein, rat; C495653:Gabpb2 protein, rat; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C489030:Tfam protein, rat; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D014284:Triiodothyronine; D025181:ATP Synthetase Complexes