Journal of Applied Physiology Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 102: 1850-1855, 2007. First published February 15, 2007; doi:10.1152/japplphysiol.01177.2006
8750-7587/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
102/5/1850    most recent
01177.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamada, T.
Right arrow Articles by Wada, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamada, T.
Right arrow Articles by Wada, M.

Myofibrillar protein oxidation and contractile dysfunction in hyperthyroid rat diaphragm

Takashi Yamada,1 Takaaki Mishima,2 Makoto Sakamoto,2 Minako Sugiyama,2 Satoshi Matsunaga,3 and Masanobu Wada1

1Graduate School of Integrated Arts and Sciences and 2Graduate School of Biosphere Science, Hiroshima University, Hiroshima; and 3Research Center for Urban Health and Sports, Osaka City University, Sugimoto, Osaka, Japan

Submitted 18 October 2006 ; accepted in final form 29 January 2007


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
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 nonselective β1- β2-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 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.

reactive oxygen species; hyperthyroidism; specific force reduction; myosin heavy chain

BREATHLESSNESS is a common complaint in patients with hyperthyroidism, and a decrease in maximum respiratory muscle strength has been reported (17, 20). Although little is known about the effects of thyroid hormone on the contractility of the respiratory muscle, reductions in the in vivo transdiaphragmatic pressure evoked by tetanic stimulation have been found in experimental hyperthyroidism (21), suggesting a loss of contractile regulation in the diaphragm. However, the mechanisms responsible for the hyperthyroid-induced diaphragmatic dysfunction are less well understood.

The cellular redox balance may have an important influence on contractile function (27). Many studies have shown that hypermetabolic state in hyperthyroidism is associated with tissue oxidative injury (5, 16, 31, 32). Lipid peroxidation in slow oxidative muscles has been shown to increase in hyperthyroid rats (4, 36). Consistent with these experiments, we previously demonstrated in the soleus muscle that 3,5,3'-triiodo-L-thyronine (T3) treatment induced both oxidation of myofibrillar proteins and reductions in specific force generation (35). However, to our knowledge, no information was given in previous studies as to whether T3 treatment increases the diaphragmatic oxidative stress and induces the impairment of contractile properties.

A number of studies have suggested that increased reactive oxygen species (ROS) production may be responsible for a component of the respiratory muscle dysfunction in some pathophysiological conditions (6, 24, 28, 30, 37, 38). In support of this contention, an exogenous ROS donor has been shown to decrease force generation in diaphragm fiber bundles (18, 29) and skinned fibers (9, 29). In addition, the role of ROS as a contributor to respiratory muscle dysfunction is emphasized by previous observations by Shindoh et al. (28) and Supinski and Callahan (30), who found that administration of antioxidants is capable of improving the force production of diaphragm in inflammatory disease processes.

As a role of ROS in muscle contractility is widely investigated, there is increasing evidence suggesting that oxidative modification of contractile and regulatory proteins is responsible for a depression in skeletal muscle force production (10, 12, 37). For instance, it is a well-known fact that alkylation of the sulfhydryl groups of myosin has significant functional effects (11). Andrade et al. (1), using intact single muscle fibers, have shown that prolonged application of hydrogen peroxide resulted in decreased force production that was accompanied by a fall in myofibrillar Ca2+ sensitivity. Moreover, they also demonstrated that functions of the sarcoplasmic reticulum are less susceptible to ROS than those of myofibrillar proteins. These findings are in agreement with the observation that, in diaphragm skinned fiber, the maximum Ca2+-activated force is decreased by the addition of an exogenous ROS donor (9, 13).

Taking these findings into account, one plausible hypothesis arises that administration of T3 may result in oxidative modifications in myofibrillar proteins and, in turn, may induce alterations in respiratory muscle function. The purpose of this study was to investigate this issue by 1) comparing protein oxidations in diaphragm muscle samples taken from control animals and T3-treated animals; and 2) examining the effect of administration of carvedilol, an antioxidant, on diaphragm force generation in animals with hyperthyroidism.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Experimental design.   Nine-week-old male Wistar rats at the beginning of the experiment were randomly assigned to one of four groups: euthyroid, hyperthyroid, euthyroid plus carvedilol, and hyperthyroid plus carvedilol. Hyperthyroidism was elicited by treatment with daily intraperitoneal injections of T3 (300 µg·kg–1·day–1) for 21 days. In this study, we employed carvedilol as an antioxidant since this agent has been shown to improve force production by preventing the oxidation of myofibrillar proteins in rat soleus muscle undergoing oxidative stress (12). Carvedilol is also a nonselective β1-β2-blocker. It is possible, therefore, that the properties of carvedilol as a β-blocker rather than an antioxidant could act on the diaphragm. However, β-blockers without known antioxidative properties have been shown to exert no effect on force production in hyperthyroidism (3, 36). Carvedilol (2 mg·kg–1·day–1) was given orally for 21 days, dissolved in ethanol and then in drinking water (ethanol final concentration 0.2%). Animals were given food and water ad libitum and housed in an environmentally controlled room (temperature, 22–25°C) with a 12:12-h light-dark cycle. At the end of a given period, rats were sedated with pentobarbital sodium (50 mg/kg). In each animal, two diaphragm bundles from left hemidiaphragm were dissected with the associated ribs and central tendon intact. One bundle was used to measure contractile function and the other to measure protein oxidation. The experimental protocol was approved by the Animal Care Committee of Hiroshima University.

Measurement of isometric contractile properties.   Isometric contractions of the diaphragm bundles were recorded in a chamber that was filled with a temperature-controlled standard solution (30°C) of the following composition (in mM): 115 NaCl, 5 KHCO3, 1 MgCl2, 20 NaHCO3, 2 CaCl2, 5 N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid, 11 glucose, 0.3 glutamic acid, and 0.38 glutamine. The solution was continuously bubbled with 95% O2-5% CO2, which gives a bath pH of 7.4. Bundles were connected to an isometric force transducer, and length was adjusted to optimize twitch force. The stimulation pulses were applied via two platinum plate electrodes placed on each side of the muscle. After 10 min of incubation, we measured isometric forces evoked by direct stimulation at 1 (evokes twitch contraction), 10, 20, 40, 75, and 100 Hz using supramaximal voltage, 1-ms pulses, and trains of 350 ms. These contractions were produced at 1-min intervals. Peak force in each contraction was measured and was normalized to cross-sectional area, where cross-sectional area was computed as muscle wet weight divided by the product of muscle length and density (1.06 g/ml).

Carbonyl content in total myofibrillar proteins.   Small muscle pieces were homogenized in a glass homogenizer in 20 volumes (wt/vol) of a solution containing (in mM) 300 KCl, 100 KH2PO4, 50 K2HPO4, and 1 EDTA (pH 6.5). The solutions were prepared with bidistilled water to limit free metal ion contamination. Just before use, the solution was stirred under vacuum and then bubbled with argon to maximally reduce the oxygen tension. The homogenate was centrifuged for 10 min at 10,000 g, and the supernatant fraction was collected as myofibrillar extracts. Protein concentration was determined according to the method of Bradford (7) using serum albumin as a standard.

The carbonyl content in total myofibrillar proteins was determined by spectrophotometry methods, as described by Levine et al. (19). Briefly, myofibril extracts containing 200 µg protein were incubated for 30 min at room temperature in 10 mM 2,4-dinitrophenylhydrazine (DNPH) in 2 N HCl. Derivatization was stopped by the addition of 20% (wt/vol) trichloroacetic acid, and protein was pelleted by centrifugation for 3 min at 11,000 g. The pellets were washed three times with ethanol-ethyl acetate (1:1). The protein was solubilized in 6 M guanidine hydrochloride in 20 mM potassium phosphate (pH 2.3). Insoluble material was removed by centrifugation, and maximal absorbance of the supernatant was measured at the wavelength of 360 nm.

Carbonyl content in myosin heavy chain.   An aliquot of myofibrillar extracts was added to 12% (wt/vol) SDS and then reacted with 20 mM DNPH for 10 min. The reaction was stopped by the addition of a solution containing 2 M Tris and 30% (vol/vol) glycerol. Aliquots of the DNPH-derivatized samples containing 1.25 µg myosin heavy chain (MHC) were applied for polyacrylamide gel electrophoresis in the presence of SDS (SDS-PAGE) as previously described in detail (33). Electrophoretically separated proteins were transferred to nitrocellulose sheets. To visualize carbonyl groups, the blots were labeled with 1:5,000 dilution of monoclonal anti-dinitrophenyl antibody coupled to alkali phosphatase (Sigma). The contents of carbonyl group in MHC were densitometrically evaluated using National Institutes of Health Image software.

MHC content in myofibrillar proteins.   To separate myofibrillar proteins, SDS-PAGE was performed using a 10–20% (wt/vol) gradient separating gel. Aliquots of myofibril extracts containing 5 µg protein were subjected to electrophoresis at 22°C for 5 h, applying a current of 20 mA. The gels were stained with Coomassie blue R in 45% (vol/vol) methanol. On the basis of densitometry of total myofibrillar proteins, the relative content occupied by MHC in myofibrillar proteins was estimated.

Statistical analyses.   A two-way variance analysis was performed to evaluate the influence of T3 and carvedilol. If an overall F value was obtained, a Scheffé's post hoc analysis was used to isolate the significantly different means. All comparisons were performed at the 95% confidence level. Data are presented as means ± SE.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Body and heart weights.   The body weights of T3-treated animals were significantly lower than those of euthyroid group (Table 1). Similar to what previous studies showed (34, 35), T3 treatment elicited significant increase in the absolute and normalized (the heart-to-body weight ratio) heart weights, suggesting that this protocol was effective in inducing a hyperthyroid state. In contrast, carvedilol treatment caused no change in body and heart weights from both euthyroid and hyperthyroid animals.


View this table:
[in this window]
[in a new window]

  		Table 1. Body and heart weights of rat groups

 
Isometric contractile force.   In agreement with a previous study (21), T3 administration induced contractile dysfunction in the diaphragm. Maximum tetanic force developed by diaphragm fiber bundles treated with T3 (1,156.4 ± 48.6 g/cm2) was less than that of euthyroid group (1,456.0 ± 49.7 g/m2) (Fig. 1). T3 treatment also decreased twitch force in diaphragm preparations (403.7 ± 29.3 vs. 623.1 ± 27.0 g/m2). Examined more broadly, hyperthyroidism led to significant reductions in force across the entire range of diaphragm activation. Administration of carvedilol had no effect on the force-frequency curve of euthyroid animals, whereas in hyperthyroid animals, carvedilol treatment significantly increased tetanic force at stimulation frequencies from 40 to 100 Hz (P < 0.05).


Figure 1
View larger version (26K):
[in this window]
[in a new window]

  		Fig. 1. Effects of 3,5,3'-triiodo-L-thyronine (T3) and carvedilol treatment on isometric forces in rat diaphragm. Hyperthyroidism was induced by daily injection of T3 for 21 days. Carvedilol was orally administered for same period. Isometric forces were evoked by direct stimulation at 1 (evokes twitch contraction), 10, 20, 40, 75, and 100 Hz. Treatment with carvedilol dramatically improved isometric tetanic force production in hyperthyroid rat diaphragm at stimulus frequencies from 40 to 100 Hz. Values are means ± SE of n = 10 per group. Groups: euthyroid (EU), euthryoid plus carvedilol (EU-CAR), hyperthyroid (HY), and hyperthyroid plus carvedilol (HY-CAR). *P < 0.05 compared with EU group; aP < 0.05 compared with EU-CAR group; bP < 0.05 compared with HY-CAR group.

 
In Table 2, we show the properties of contraction and relaxation in isometric force of diaphragm preparation. The tetanic parameters were obtained from stimulus frequency at 40 Hz where tension was significantly reduced in hyperthyroid animals compared with the other three groups. Twitch contraction time was shorter in hyperthyroid animals than in euthyroid and carvedilol-treated euthyroid animals. In contrast, the rate of contraction and relaxation from twitch and tetanic forces did not show any significant differences among the four groups.


View this table:
[in this window]
[in a new window]

  		Table 2. Contractile properties of diaphragm bundles of rat groups

 
Carbonyl group content.   T3 administration resulted in an ~2-fold increase (P < 0.05) in the carbonyl content in diaphragmatic myofibrillar proteins compared with the euthyroid group (2.71 ± 0.37 vs. 5.54 ± 0.63 nmol/mg protein) (Fig. 2). Administration of carvedilol had no effect on the carbonyl content in euthyroid animals, whereas carvedilol treatment dramatically reduced the level of myofibrillar protein oxidation in hyperthyroid animals (P < 0.05). Figure 3A shows the representative Western blots illustrating the carbonyl content in MHC. The densitometric evaluation of the blot revealed that treatment with T3 or carvedilol evoked no changes in the carbonyl content in MHC (Fig. 3B).


Figure 2
View larger version (16K):
[in this window]
[in a new window]

  		Fig. 2. Effects of T3 and carvedilol treatment on carbonyl content in myofibrillar proteins in rat diaphragm. The carbonyl contents were evaluated by the spectrophotometric assay by using 2,4-dinitrophenylhydrazine. Values are means ± SE of n = 10 per group. *P < 0.05 compared with other 3 groups.

 

Figure 3
View larger version (35K):
[in this window]
[in a new window]

  		Fig. 3. Immunoblot analyses (A) and carbonyl content (B) of myosin heavy chain (MHC) in rat diaphragm. A: immunoblots labeled with monoclonal antibody against dinitrophenyl. B: carbonyl contents were evaluated by the densitometry of immunoblots. Results are expressed as a percentage of EU value. Values are means ± SE of n = 10 per group.

 
MHC content in myofibrillar proteins.   There were no significant differences in the concentration of myofibrillar proteins among all groups (results not shown). In contrast, T3 treatment resulted in significant reductions (P < 0.05) in the relative concentration of MHC in total myofibrillar proteins compared with euthyroid animals given carvedilol (Fig. 4).


Figure 4
View larger version (18K):
[in this window]
[in a new window]

  		Fig. 4. Effects of T3 and carvedilol treatment on MHC content in total myofibrillar proteins in rat diaphragm. Myofibrillar proteins were separated by using polyacrylamide gradient (10–20%) gel electrophoresis and evaluated densitometrically. The MHC content is expressed as a percentage of total myofibrillar proteins. Values are means ± SE of n = 10 per group. *P < 0.05 compared with EU-CAR group.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study provides the first evidence that, in hyperthyroid rat diaphragm, the myofibrillar proteins exhibit increased levels of oxidative stress, and carvedilol, an antioxidant, is capable of preventing both contractile dysfunction and oxidation of myofibrillar proteins. These data suggest that the oxidative modification of myofibrillar proteins may account, at least in part, for an impairment of diaphragm in hyperthyroidism.

T3-induced oxidative stress in diaphragm.   Available data indicate that hyperthyroid tissues exhibit an increased ROS production, as documented by enhanced levels of indicators of lipid and protein oxidation (reviewed in Ref. 32). In both rat (4) and cat (36), T3-induced increases in lipid peroxidation were found in the soleus composed mainly of slow-twitch oxidative fibers but not in the extensor digitorum longus composed mainly of fast-twitch glycolytic fibers. Taken together, it is conceivable that the degree of T3-induced oxidative modifications correlates with properties in oxidative metabolism in muscles, given that these effects seem to be primarily determined through increased mitochondrial production of ROS. Our results demonstrated for the first time that protein oxidation occurs in hyperthyroid diaphragm, which is composed predominantly of glycolytic fibers. The reason for the oxidation of diaphragm remains unknown, but this discrepancy could be explained by the fact that the diaphragm contains relatively large amounts of mitochondria compared with locomotor muscles consisting of similar fiber-type composition (8).

Diaphragmatic force production in hyperthyroidism.   While a locomotor muscle weakness is frequently recognized (25, 26, 39), respiratory muscle function has not hitherto been studied in detail in hyperthyroidism. It has been shown in experimental hyperthyroidism that microscopic examination reveals atrophy of diaphragm muscle fiber, indicating that loss of muscle mass may account for decreased muscle contractility (21). However, our results of the marked depression in isometric forces, even after data were corrected for differences in muscle cross-sectional area, suggest that hyperthyroid-induced diaphragmatic contractile dysfunctions result not only from muscle atrophy but also from the failure in the muscle force-generating capacity.

There are several theoretical processes that could account for reductions in muscle specific force generation. For one thing, Shindoh et al. (28) and Supinski and Callahan (30) have shown that some inflammatory diseases, including sepsis and heart failure, associated with the development of generalized muscle weakness evoke increased ROS production in skeletal muscle. These previous studies also demonstrated that administration of an exogenous ROS scavenger prevented lipid peroxidation and contractile dysfunction in skeletal muscle. Taking these findings into account, it would appear that free radical-mediated oxidative modification may contribute to reductions in skeletal muscle force generation.

There has been no previous demonstration, however, of a role of oxidation in diaphragm in an animal model of hyperthyroidism. Our data provide the first evidence that administration of carvedilol is capable of preventing both hyperthyroid-induced protein oxidation and reductions in specific force generation. Because carvedilol is a widely used β-blocker that possesses antioxidative properties (12), it is possible that their antiadrenergic activity could influence the improvement of diaphragm dysfunction in our animal model. However, this possibility seems remote because previous studies have revealed that β-blockers such as metoprolol and propranolol, without known antioxidative properties, have no effect on muscle weakness and wasting in hyperthyroidism (3, 36).

T3-induced myofibrillar protein oxidation.   There are a number of studies indicating that oxidative modifications of myofibrillar proteins have a large impact on the function of skeletal muscle (1, 2, 22, 23). Myofibrillar proteins appear to exhibit high sensitivity to redox modulation (10, 12, 37). For instance, Zergeroglu et al. (37) studied the effects of mechanical ventilation, which evokes protein oxidation and contractile dysfunction, on entire proteins in diaphragm and found more severe oxidation in myofibrillar proteins than in others. It is still an open question which proteins constituting the myofibrillar complex are primarily influenced by changes in intracellular redox balance. As previously shown by our carbonyl data, MHC, the most abundant protein in myofibrils, is highly susceptible to oxidation in hyperthyroid rat soleus (35). The alterations in carbonyl groups were accompanied by reductions in MHC protein content (35). It has been hypothesized that enhanced carbonylation may trigger protein degradation (35), as carbonylation is characterized by an irreversible modification that requires the proteolytic removal followed by the resynthesis of the affected protein (14). Our results of the changes in the protein and carbonyl contents of MHC resemble, at least qualitatively, those occurring in the soleus, although the elevation in the carbonyl content did not reach a significant level. Alternatively, our data imply that diaphragm and limb muscle could differ with regard to their responses to oxidative stress, although the mechanism is unclear.

The depressions in force production observed in the diaphragm could be explained by alterations in myofibrillar Ca2+-sensitivity. Moopanar and Allen (22, 23) found that repetitive contraction decreased force in the absence of tetanic Ca2+ concentration in the myoplasm and suggested that ROS, the production of which is elevated by muscle activity, might elicit oxidative modification of troponins I and C, leading to loss of Ca2+ sensitivity (15). On the basis of these findings, it is speculated that treatment with carvedilol could prevent or attenuate T3-induced oxidative damage of regulatory proteins in the myofibril.

In conclusion, we have presented data suggesting that hyperthyroid-induced loss of respiratory muscle strength may be ascribed to oxidative modification in myofibrillar proteins. A possible role of ROS in hyperthyroid rat diaphragm weakness is further supported by the observations showing that exogenous administration of antioxidant prevents both myofibrillar oxidation and reduction in specific force generation. Moreover, the fact that there is no overt loss of myofibrillar proteins in hyperthyroid animals argues that, in early stages of hyperthyroidism, contractile dysfunction in diaphragm does not result from protein degradation but more likely results from the failure in the force-generation capacities. Although the present experiment revealed that MHC is the unlikely target of ROS in diaphragm, additional work is required to determine whether T3-induced ROS production could affect other proteins in myofibrils and induce contractile dysfunctions.


   FOOTNOTES
 

Address for reprint requests and other correspondence: M. Wada, Graduate School of Integrated Arts and Sciences, Hiroshima Univ., 1-7-1, Higashihiroshima-shi, Hiroshima, Japan 739-8521 (e-mail: wada{at}hiroshima-u.ac.jp)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Andrade FH, Reid MB, Allen DG, Westerblad H. Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse. J Physiol 509: 565–575, 1998.[Abstract/Free Full Text]
  2. Andrade FH, Reid MB, Westerblad H. Contractile response of skeletal muscle to low peroxide concentrations: myofibrillar calcium sensitivity as a likely target for redox-modulation. FASEB J 15: 309–311, 2001.[Free Full Text]
  3. Angeras U, Hasselgren PO. Protein degradation in skeletal muscle during experimental hyperthyroidism in rats and the effect of beta-blocking agents. Endocrinology 120: 1417–1421, 1987.[Abstract/Free Full Text]
  4. Asayama K, Dobashi K, Hayashibe H, Megata Y, Kato K. Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology 121: 2112–2118, 1987.[Abstract/Free Full Text]
  5. Asayama K, Kato K. Oxidative muscular injury and its relevance to hyperthyroidism. Free Radic Biol Med 8: 293–303, 1990.[CrossRef][Web of Science][Medline]
  6. Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, Gea J. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 171: 1116–1124, 2005.[Abstract/Free Full Text]
  7. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976.[CrossRef][Web of Science][Medline]
  8. Caillaud C, Py G, Eydoux N, Legros P, Prefaut C, Mercier J. Antioxidants and mitochondrial respiration in lung, diaphragm, and locomotor muscles: effect of exercise. Free Radic Biol Med 26: 1292–1299, 1999.[CrossRef][Web of Science][Medline]
  9. Callahan LA, She ZW, Nosek TM. Superoxide, hydroxyl radical, and hydrogen peroxide effects on single-diaphragm fiber contractile apparatus. J Appl Physiol 90: 45–54, 2001.[Abstract/Free Full Text]
  10. Canton M, Neverova I, Menabò R, Van Eyk J, Di Lisa F. Evidence of myofibrillar protein oxidation induced by postischemic reperfusion in isolated rat hearts. Am J Physiol Heart Circ Physiol 286: H870–H877, 2004.[Abstract/Free Full Text]
  11. Crowder MS, Cooke R. The effect of myosin sulphydryl modification on the mechanics of fibre contraction. J Muscle Res Cell Motil 5: 131–146, 1984.[CrossRef][Web of Science][Medline]
  12. Dalla Libera L, Ravara B, Gobbo V, Danieli Betto D, Germinario E, Angelini A, Vescovo G. Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol. J Mol Cell Cardiol 38: 803–807, 2005.[CrossRef][Web of Science][Medline]
  13. Darnley GM, Duke AM, Steele DS, MacFarlane NG. Effects of reactive oxygen species on aspects of excitation-contraction coupling in chemically skinned rabbit diaphragm muscle fibres. Exp Physiol 86: 161–168, 2001.[Abstract]
  14. Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 324: 1–8, 1997.[Web of Science][Medline]
  15. De Paula Brotto M, van Leyen SA, Brotto LS, Jin JP, Nosek CM, Nosek TM. Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights into physiologic muscle fatigue. Pflügers Arch 442: 738–744, 2001.[CrossRef][Web of Science][Medline]
  16. Duntas LH. Oxidants, antioxidants in physical exercise and relation to thyroid function. Horm Metab Res 37: 572–576, 2005.[CrossRef][Web of Science][Medline]
  17. Kahaly GJ, Nieswandt J, Wagner S, Schlegel J, Mohr-Kahaly S, Hommel G. Ineffective cardiorespiratory function in hyperthyroidism. J Clin Endocrinol Metab 83: 4075–4078, 1998.[Abstract/Free Full Text]
  18. Lawler JM, Cline CC, Hu Z, Coast JR. Effect of oxidative stress and acidosis on diaphragm contractile function. Am J Physiol Regul Integr Comp Physiol 273: R630–R636, 1997.[Abstract/Free Full Text]
  19. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186: 464–478, 1990.[Medline]
  20. Mier A, Brophy C, Wass JA, Besser GM, Green M. Reversible respiratory muscle weakness in hyperthyroidism. Am Rev Respir Dis 139: 529–533, 1989.[Web of Science][Medline]
  21. Miyashita A, Suzuki S, Suzuki M, Numata H, Suzuki J, Akahori T, Okubo T. Effect of thyroid hormone on in vivo contractility of the canine diaphragm. Am Rev Respir Dis 145: 1452–1462, 1992.[Medline]
  22. Moopanar TR, Allen DG. Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse skeletal muscle at 37°C. J Physiol 564: 189–199, 2005.[Abstract/Free Full Text]
  23. Moopanar TR, Allen DG. The activity-induced reduction of myofibrillar Ca2+ sensitivity in mouse skeletal muscle is reversed by dithiothreitol. J Physiol 571: 191–200, 2006.[Abstract/Free Full Text]
  24. Nethery D, DiMarco A, Stofan D, Supinski G. Sepsis increases contraction-related generation of reactive oxygen species in the diaphragm. J Appl Physiol 87: 1279–1286, 1999.[Abstract/Free Full Text]
  25. Nørrelund H, Hove KY, Brems-Dalgaard E, Jurik AG, Nielsen LP, Nielsen S, Jørgensen JO, Weeke J, Moller N. Muscle mass and function in thyrotoxic patients before and during medical treatment. Clin Endocrinol (Oxf) 51: 693–699, 1999.[CrossRef][Medline]
  26. Ramsay ID. Muscle dysfunction in hyperthyroidism. Lancet 2: 931–934, 1966.[Web of Science][Medline]
  27. Reid MB. Redox modulation of skeletal muscle contraction: what we know and what we don't. J Appl Physiol 90: 724–731, 2001.[Abstract/Free Full Text]
  28. Shindoh C, DiMarco A, Nethery D, Supinski G. Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin. Am Rev Respir Dis 145: 1350–1354, 1992.[Web of Science][Medline]
  29. Supinski G, Stofan D, Callahan LA, Nethery D, Nosek TM, DiMarco A. Peroxynitrite induces contractile dysfunction and lipid peroxidation in the diaphragm. J Appl Physiol 87: 783–791, 1999.[Abstract/Free Full Text]
  30. Supinski GS, Callahan LA. Diaphragmatic free radical generation increases in an animal model of heart failure. J Appl Physiol 99: 1078–1084, 2005.[Abstract/Free Full Text]
  31. Venditti P, Balestrieri M, Di Meo S, De Leo T. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. J Endocrinol 155: 151–157, 1997.[Abstract/Free Full Text]
  32. Venditti P, Di Meo S. Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63: 414–434, 2006.[CrossRef][Web of Science][Medline]
  33. Wada M, Okumoto T, Toro K, Masuda K, Fukubayashi T, Kikuchi K, Niihata S, Katsuta S. Expression of hybrid isomyosins in human skeletal muscle. Am J Physiol Cell Physiol 271: C1250–C1255, 1996.[Abstract/Free Full Text]
  34. Yamada T, Inashima S, Matsunaga S, Nara I, Kajihara H, Wada M. Different time course of changes in sarcoplasmic reticulum and myosin isoforms in rat soleus muscle at early stage of hyperthyroidism. Acta Physiol Scand 180: 79–87, 2004.[CrossRef][Web of Science][Medline]
  35. Yamada T, Mishima T, Sakamoto M, Sugiyama M, Matsunaga S, Wada M. Oxidation of myosin heavy chain and reduction in force production in hyperthyroid rat soleus. J Appl Physiol 100: 1520–1526, 2006.[Abstract/Free Full Text]
  36. Zaiton Z, Merican Z, Khalid BA, Mohamed JB, Baharom S. The effects of propranolol on skeletal muscle contraction, lipid peroxidation products and antioxidant activity in experimental hyperthyroidism. Gen Pharmacol 24: 195–199, 1993.[Web of Science][Medline]
  37. Zergeroglu MA, McKenzie MJ, Shanely RA, Van Gammeren D, DeRuisseau KC, Powers SK. Mechanical ventilation-induced oxidative stress in the diaphragm. J Appl Physiol 95: 1116–1124, 2003.[Abstract/Free Full Text]
  38. Zuo L, Christofi FL, Wright VP, Liu CY, Merola AJ, Berliner LJ, Clanton TL. Intra- and extracellular measurement of reactive oxygen species produced during heat stress in diaphragm muscle. Am J Physiol Cell Physiol 279: C1058–C1066, 2000.[Abstract/Free Full Text]
  39. Zurcher RM, Horber FF, Grunig BE, Frey FJ. Effect of thyroid dysfunction on thigh muscle efficiency. J Clin Endocrinol Metab 69: 1082–1086, 1989.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Eur Respir JHome page
F. Laghi, N. Adiguzel, and M. J. Tobin
Endocrinological derangements in COPD
Eur. Respir. J., October 1, 2009; 34(4): 975 - 996.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
102/5/1850    most recent
01177.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamada, T.
Right arrow Articles by Wada, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamada, T.
Right arrow Articles by Wada, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.