Submitted on October 18, 2006
Accepted on January 29, 2007
Myofibrillar protein oxidation and contractile dysfunction in hyperthyroid rat diaphragm
Takashi Yamada1, Takaaki Mishima2, Makoto Sakamoto2, Minako Sugiyama2, Satoshi Matsunaga3, and Masanobu Wada4*
1 Graduate School of Integrated Arts and Sciences, Hiroshima university, Higashihiroshima, Hiroshima, Japan
2 Graduate school of biophere science, Hiroshima university, higashihiroshima, Hiroshima, Japan
3 Research Center for Urban Health and Sports, Osaka City University, Osaka, Japan
4 Faculty of Integrated Arts and Sciences, Health and Sport Science, Higashihiroshima, Japan
* To whom correspondence should be addressed. E-mail: wada{at}hiroshima-u.ac.jp.
The purpose of the present study was to test the hypothesis that administration of
thyroid hormone [3,5,3'-triiodo-L-thyronine (T3)] could result in oxidation of myofibrillar proteins and, in turn, induce alterations in respiratory muscle function. Daily injection of T3 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, T3 treatment has no effects on the carbonyl content in myosin heavy chain. In additional experiments, we have also tested the efficacy of carvedilol, a non-selective 
1-2-blocker which possesses anti-oxidative properties. Treatment with carvedilol dramatically improved isometric tetanic force production at stimulus frequencies from 40 to 100 Hz (P < 0.05). Carvedilol also prevented T3-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.
