Oxidation of myosin heavy chain and reduction in force production in hyperthyroid rat soleus.
We tested the hypothesis that a force reduction in hyperthyroid rat soleus muscle would be associated with oxidative modification in myosin heavy chain (MHC). Daily injection of thyroid hormone [3,5,3'-triiodo-L-thyronine (T3)] for 21 days depressed isometric forces of whole soleus muscle across a range of stimulus frequencies (P < 0.01). In fiber bundles, hyperthyroidism also led to pronounced reductions (P < 0.01) in both K+ - and 4-chloro-m-cresol-induced contracture forces. The degrees of the reductions were similar between these two contractures that were induced by distinct reagents. Treatment with T3 elicited a significant decrease ( approximately 14%; P < 0.05) in the relative content of MHC contained in myofibrillar proteins. The content of carbonyl groups in myofibrillar protein extracts was elevated (P < 0.05) by approximately 50% in T3-treated muscles. Immunoblot analyses on T3-treated muscles showed a greater increase (106%; P < 0.05) of the carbonyl content in MHC than in myofibrillar protein extracts. These data suggest that in hyperthyroidism the decrease in force production of skeletal muscles may stem primarily from failure in myofibrillar protein function resulting from oxidative modification of MHC.
Yamada
Takashi
T
Graduate School of Biosphere Science, Hiroshima University, Hiroshima, Japan.
Mishima
Takaaki
T
Sakamoto
Makoto
M
Sugiyama
Minako
M
Matsunaga
Satoshi
S
Wada
Masanobu
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003408:Cresols / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D006980:Hyperthyroidism / Q000150:complications*; D015151:Immunoblotting; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018908:Muscle Weakness / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology; D018995:Myosin Heavy Chains / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology
D003408:Cresols; D017382:Reactive Oxygen Species; D014284:Triiodothyronine; C006984:chlorocresol; D018995:Myosin Heavy Chains; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D011188:Potassium