Myofibrillar protein oxidation and contractile dysfunction in hyperthyroid rat diaphragm.
The purpose of the present study was to test the hypothesis that administration of thyroid hormone [3,5,3'-triiodo-L-thyronine (T(3))] could result in oxidation of myofibrillar proteins and, in turn, induce alterations in respiratory muscle function. Daily injection of T(3) for 21 days depressed isometric forces of diaphragm fiber bundles across a range of stimulus frequencies (1, 10, 20, 40, 75, and 100 Hz) (P < 0.05). These reductions in force production were accompanied by a remarkable increment (104%; P < 0.05) in carbonyl groups of myofibrillar proteins. In contrast, T(3) treatment has no effects on the carbonyl content in myosin heavy chain. In additional experiments, we have also tested the efficacy of carvedilol, a nonselective beta(1)- beta(2)-blocker that possesses antioxidative properties. Treatment with carvedilol dramatically improved isometric tetanic force production at stimulus frequencies from 40 to 100 Hz (P < 0.05). Carvedilol also prevented T(3)-induced contractile protein oxidation (P < 0.05). These data suggest that the oxidative modification of myofibrillar proteins may account, at least in part, for an impairment of diaphragm in hyperthyroidism.
Yamada
Takashi
T
Graduate School of Integrated Arts and Sciences, Hiroshima University, Japan 739-8521.
Mishima
Takaaki
T
Sakamoto
Makoto
M
Sugiyama
Minako
M
Matsunaga
Satoshi
S
Wada
Masanobu
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014284:Triiodothyronine
D000975:Antioxidants; D002227:Carbazoles; D009124:Muscle Proteins; D011412:Propanolamines; D017382:Reactive Oxygen Species; D014284:Triiodothyronine; D000077261:Carvedilol; D018995:Myosin Heavy Chains