Myofibrillar protein oxidation and contractile dysfunction in hyperthyroid rat diaphragm

2007 ◽  
Vol 102 (5) ◽  
pp. 1850-1855 ◽  
Author(s):  
Takashi Yamada ◽  
Takaaki Mishima ◽  
Makoto Sakamoto ◽  
Minako Sugiyama ◽  
Satoshi Matsunaga ◽  
...  

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.

2006 ◽  
Vol 100 (5) ◽  
pp. 1520-1526 ◽  
Author(s):  
Takashi Yamada ◽  
Takaaki Mishima ◽  
Makoto Sakamoto ◽  
Minako Sugiyama ◽  
Satoshi Matsunaga ◽  
...  

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 (∼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 ∼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.


Cellulose ◽  
2020 ◽  
Vol 27 (15) ◽  
pp. 8977-8987
Author(s):  
Floriana Coppola ◽  
Alberto Modelli

Abstract The degradation of paper-based materials involves several and complex mechanisms, such as hydrolysis and oxidation. The behaviour of different types of pulps can be very variable. In this study, the difference upon oxidation of contemporary non-recycled and recycled papers, which now constitute a considerable fibre source, is investigated. A 0.015 M potassium periodate solution is used to oxidise five types of paper, two non-recycled and three recycled, for 0.5, 1, 2 and 4 h. The effects of such oxidation treatments are evaluated in terms of carbonyl content and degree of polymerisation (DP). A modified procedure of the Szabolcs’s method and viscometry are used to measure the carbonyl content and DP, respectively. The carbonyl groups are found to increase more rapidly in the recycled papers than in the non-recycled ones. On the contrary, oxidation causes a larger decrease of the DP values in the non-recycled papers, the paper made of pure cellulose being the most sensitive in terms of depolymerisation. The DP values measured for pure cellulose paper are in line with previously reported data. Moreover, in accordance with the Ekenstam equation, the plots of the reciprocal of DP as a function of oxidation time show good linear correlations for all types of paper investigated. Pseudo rate constants are thus calculated from the slopes of these plots, those of the non-recycled papers being found to be higher than those of the recycled papers. Graphic abstract


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricarda M. Haeger ◽  
Dilson E. Rassier

AbstractWhen a muscle is stretched during a contraction, the resulting steady-state force is higher than the isometric force produced at a comparable sarcomere length. This phenomenon, also referred to as residual force enhancement, cannot be readily explained by the force-sarcomere length relation. One of the most accepted mechanisms for the residual force enhancement is the development of sarcomere length non-uniformities after an active stretch. The aim of this study was to directly investigate the effect of non-uniformities on the force-producing capabilities of isolated myofibrils after they are actively stretched. We evaluated the effect of depleting a single A-band on sarcomere length non-uniformity and residual force enhancement. We observed that sarcomere length non-uniformity was effectively increased following A-band depletion. Furthermore, isometric forces decreased, while the percent residual force enhancement increased compared to intact myofibrils (5% vs. 20%). We conclude that sarcomere length non-uniformities are partially responsible for the enhanced force production after stretch.


1997 ◽  
Vol 78 (2) ◽  
pp. 1170-1174 ◽  
Author(s):  
Lauren E. Sergio ◽  
John F. Kalaska

Sergio, Lauren E. and John F. Kalaska. Systematic changes in directional tuning of motor cortex cell activity with hand location in the workspace during generation of static isometric forces in constant spatial directions. J. Neurophysiol. 78: 1170–1174, 1997. We examined the activity of 46 proximal-arm-related cells in the primary motor cortex (MI) during a task in which a monkey uses the arm to exert isometric forces at the hand in constant spatial directions while the hand is in one of nine different spatial locations on a plane. The discharge rate of all 46 cells was significantly affected by both hand location and by the direction of static force during the final static-force phase of the task. In addition, all cells showed a significant interaction between force direction and hand location. That is, there was a significant modulation in the relationship between cell activity and the direction of exerted force as a function of hand location. For many cells, this modulation was expressed in part as a systematic arclike shift in the cell's directional tuning at the different hand locations, even though the direction of static force output at the hand remained constant. These effects of hand location in the workspace indicate that the discharge of single MI cells does not covary exclusively with the level and direction of force output at the hand. Sixteen proximal-arm-related muscles showed similar effects in the task, reflecting their dependence on various mechanical factors that varied with hand location. The parallel changes found for both MI cell activity and muscle activity for static force production at different hand locations are further evidence that MI contributes to the transformation between extrinsic and intrinsic representations of limb movement.


1993 ◽  
Vol 264 (1) ◽  
pp. C19-C26 ◽  
Author(s):  
A. Horowitz ◽  
G. H. Pollack

The higher force observed in fixed-end tetani relative to sarcomere-isometric tetani is commonly attributed to sarcomere length inhomogeneity; sarcomeres in the end regions of the fiber shorten extensively at the expense of the central sarcomeres. By shortening, these sarcomeres supposedly attain higher force production capacity and can thus account for the extra force. However, the fibers could also contain sarcomeres that stay isometric throughout most of the tetanic force plateau. If such sarcomeres undergo slight shortening before their isometric phase, their force-length relation should be elevated (A. Horowitz, H. P. M Wussling, and G. H. Pollack. Biophys. J. 63: 3-17, 1992). These sarcomeres may therefore account for the higher force in fixed-end tetani. To test this possibility, single frog semitendinosus fibers were tetanized under fixed-end conditions. Sarcomere length change during the tetanus was measured at different locations along the fiber by optical diffraction. Fibers stretched to average sarcomere lengths between 2.2 and 3.2 microns contained sarcomeres that, except for some initial shortening during the early part of the tetanus, remained isometric. These sarcomeres were located between the ends and the central region of the fibers. Their force-length relation was higher than the linear force-length relation based on sarcomere length clamps by an average of 14% between sarcomere lengths of 2.4-3.2 microns. Thus slight (1-5%) shortening may explain the relatively higher fixed-end force-length relation.


2005 ◽  
Vol 98 (5) ◽  
pp. 1753-1760 ◽  
Author(s):  
V. P. Wright ◽  
P. F. Klawitter ◽  
D. F. Iscru ◽  
A. J. Merola ◽  
T. L. Clanton

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of Pi. Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 μM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca2+ concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to ∼10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Piming Zhao ◽  
Li Xu ◽  
Younss Ait-Mou ◽  
Pieter P. de Tombe ◽  
Renzhi Han

Dysferlin plays an important role in repairing membrane damage elicited by laser irradiation, and dysferlin deficiency causes muscular dystrophy and associated cardiomyopathy. Proteins such as perforin, complement component C9, and bacteria-derived cytolysins, as well as the natural detergent saponin, can form large pores on the cell membrane via complexation with cholesterol. However, it is not clear whether dysferlin plays a role in repairing membrane damage induced by pore-forming reagents. In this study, we observed that dysferlin-deficient muscles recovered the tetanic force production to the same extent as their WT counterparts following a 5-min saponin exposure (50 μg/mL). Interestingly, the slow soleus muscles recovered significantly better than the fastextensor digitorum longus(EDL) muscles. Our data suggest that dysferlin is unlikely involved in repairing saponin-induced membrane damage and that the slow muscle is more efficient than the fast muscle in repairing such damage.


2010 ◽  
Vol 109 (6) ◽  
pp. 1716-1727 ◽  
Author(s):  
Cecilia McCormick ◽  
Leo Alexandre ◽  
Juliette Thompson ◽  
Gabriel Mutungi

Although the acute actions of short-acting β2-adrenoceptor agonists on force production in isolated mammalian skeletal muscle fibers have been the subject of a number of previous studies, those of long-acting β2-adrenoceptor agonists have never been investigated. Also, little is known about the cellular signal transduction events mediating their actions. Therefore, the primary aim of this study was to investigate the acute effects of treatment of mouse fast- and slow-twitch muscle fiber bundles with clenbuterol, formoterol, and salbutamol. Both clenbuterol and salbutamol increased the levels of cAMP in both fiber types, and this effect was reversed by ICI-118551. On the other hand, clenbuterol and formoterol decreased force production in both fiber types. They also increased the phosphorylation of phospholamban and β2-adrenoceptors in slow-twitch fiber bundles, and their effects were insensitive to propranolol, ICI-118551, and 14–22 amide. In contrast, salbutamol increased force production in both fiber types. It also increased the phosphorylation of β2-adrenoceptors in slow-twitch fibers only, but it had no effect on the phosphorylation of phospholamban in either fiber type. These effects were reversed by propranolol and ICI-118551 but not by 14–22 amide. Instead, 14–22 amide further potentiated the effects of salbutamol on force. In summary, long- and short-acting β2-adrenoceptor agonists have opposite effects on force production in isolated intact mouse skeletal muscle fiber bundles. From these results, we suggest that the acute actions of short-acting β2-adrenoceptor agonists on force production in mammalian skeletal muscles are mediated through the β2-adrenoceptor, whereas those of long-acting β2-adrenoceptor agonists are not.


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