Thyroid hormone increases transcription of GA-binding protein/nuclear respiratory factor-2 alpha-subunit in rat liver

FEBS Lett. 2002 Mar 13;514(2-3):309-14. doi: 10.1016/s0014-5793(02)02389-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes / genetics
  • ATP Synthetase Complexes / metabolism
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Administration Schedule
  • GA-Binding Protein Transcription Factor
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hypothyroidism / drug therapy
  • Hypothyroidism / metabolism
  • Injections, Intraperitoneal
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mitochondrial Proteins*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / drug effects*
  • Triiodothyronine / administration & dosage*

Substances

  • DNA-Binding Proteins
  • GA-Binding Protein Transcription Factor
  • Gabpa protein, rat
  • Gabpb2 protein, rat
  • Mitochondrial Proteins
  • Nuclear Proteins
  • Protein Subunits
  • RNA, Messenger
  • Tfam protein, rat
  • Transcription Factors
  • mitochondrial transcription factor A
  • Triiodothyronine
  • ATP Synthetase Complexes