Item – Theses Canada

OCLC number
56874207
Link(s) to full text
LAC copy
LAC copy
Author
Sheehan, Treacey,1975-
Title
The thyroid hormone-induced coordination of cytochrome c oxidase subunit expression is tissue-specific.
Degree
M. Sc. -- York University, 2003
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2004]
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
Thyroid hormone (T3) has a dominant influence on metabolic rate. The control of T3 over mitochondrial respiration is partly mediated via its action on the cytochrome c oxidase (COX) enzyme, a multi-subunit complex of the respiratory chain. We investigated the expression of COX subunits I, III, Vb, and VIc to 5 days of T3 treatment. Furthermore, we also investigated the expression of two ubiquitously expressed thyroid receptors (TR)[alpha]1 and TR[beta]1 in response to T3. We assessed whether these alterations paralleled functional changes in the COX holoenzyme by measuring its activity. T3 treatment induced TR[beta]1 expression 1.6-fold in liver and soleus while TR[alpha]1 expression remained unchanged. Concomitant increases in the protein and mRNA expression of nuclear-encoded subunit COX Vb occurred in soleus, plantaris, and liver in response to T3. This was matched by a 1.3-fold increase in TR binding to the TRE in the COX Vb promoter in liver, suggesting transcriptional regulation. However, binding to the TRE decreased in soleus and plantaris, despite increases in COX Vb mRNA and protein suggesting the existence of other regulatory factors involved in this subunits expression. COX VIc protein levels also increased in soleus and plantaris, but to a lesser extent than for COX Vb. T3 induced increases in mitochondrially-encoded COX III mRNA in soleus, plantaris, and liver. However, binding of the mitochondrial TR p43 to mtDNA was unaltered (plantaris, liver, heart) or decreased (32%, soleus; p < 0.05). COX I protein was increased 1.2-1.7-fold in all tissues, and most closely paralleled the changes in COX activity produced by T3. Thus, COX subunits are differentially regulated by T3 in a tissue-specific manner. Increases in COX activity closely matched changes in expression of the COX subunits in liver, plantaris, and soleus, but not in heart. Finally, the data suggest that COX subunits are regulated at the level of transcription, as well as by mRNA stability.
ISBN
0612829545
9780612829541