Effects of 3,3',5-triiodo-L-thyronine (L-T3) and T3 analogues on mitochondrial function.
The effects of L-T3 and several analogues on mitochondrial parameters were determined in hypothyroid rats. These parameters include the 24 hour hormone-induced changes in the bc1 complex and in the inner membrane's proton permeability. L-T3, and all analogues except rT3, increased mitochondrial ubiquinone to euthyroid levels. L-T3, D-T3 and 3'IpT2 but not rT3, Triac, Triprop, or Dimit, altered the bypass respiration in the bc1 complex. L-T3, D-T3, Triac, 3'IpT2, and Triprop, but not rT3 or Dimit, increased the membrane's proton permeability. Actinomycin D did not prevent the increase in mitochondrial ubiquinone or the permeability change. The results show the selective thyromimetic properties of the analogues and that some of the mitochondrial changes do not require protein synthesis.
Horrum
M A
MA
Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA.
Tobin
R B
RB
Ecklund
R E
RE
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003575:Cytochromes c1 / Q000187:drug effects / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007037:Hypothyroidism / Q000188:drug therapy / Q000503:physiopathology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D017494:Proton Pumps / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000032:analysis / Q000494:pharmacology*; D014285:Triiodothyronine, Reverse / Q000494:pharmacology*; D014451:Ubiquinone / Q000032:analysis
D017494:Proton Pumps; D014284:Triiodothyronine; D014451:Ubiquinone; D003609:Dactinomycin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D014285:Triiodothyronine, Reverse; D003575:Cytochromes c1; D005993:Glycerolphosphate Dehydrogenase