Effects of the novel thyroid hormone analogues, SKF L-94901, DIBIT, and 3'-AC-T2 on mitochondrial function.
The effects of L-T3 (3,3',5-triiodo-L-thyronine) and three novel analogues, SKF L-94901 (3,5-Dibromo-3'-pyridazinone-L-thyronine), Dibit (3,5-Dibromo-3'-isopropyl-L-thyronine), and 3'-Ac-T2(3'-Acetyl-3,5,-Diiodo-L-thyronine), on mitochondrial parameters were determined in hypothyroid rats. The parameters include the 24 hour hormone-induced changes in the bc1 complex and in the proton permeability of the mitochondrial inner membrane. The cardiac sparing analogue, SKF L-94901, had no effect on mitochondrial respiration or proton permeability; but the analogue did increase a-glycerophosphate dehydrogenase activity, mitochondrial ubiquinone content, and altered the bypass respiration in the bc1 complex. Dibit also did not increase respiration significantly but did change the other parameters. 3'-Ac-T2 increased respiration, mitochondrial ubiquinone content, proton permeability, enzyme activity and altered the bypass of the Antimycin A blockage in the bc1 complex.
Horrum
M A
MA
Research Service, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha 68105, USA.
Tobin
R B
RB
Ecklund
R E
RE
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004104:Diiodothyronines / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013970:Thyronines / Q000494:pharmacology*; D014451:Ubiquinone / Q000378:metabolism
D004104:Diiodothyronines; D011522:Protons; C050835:SK&F 94901; D013970:Thyronines; D014451:Ubiquinone; C104932:3,5-dibromo-3'-isopropylthyronine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C042998:3'-acetyl-3,5-diiodothyronine; D005993:Glycerolphosphate Dehydrogenase