Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myofibrillar proteins exist as multiple isoforms that derive from multigene (isogene) families. Additional isoforms, including products of tropomyosin, myosin light chain 1 fast, troponin T, titin, and nebulin genes, can be generated from the same gene through alternative splicing or use of alternative promoters. Myofibrillar protein isogenes are differentially expressed in various muscle types and fiber types but can be coexpressed within the same fiber. Isogenes are regulated by transcriptional and posttranscriptional mechanisms; however, specific regulatory sequences and transcriptional factors have not yet been identified. The pattern of isogene expression varies during muscle development in relation to the different origin of myogenic cells and primary/secondary fiber generations and is affected by neural and hormonal influences. The variable expression of myofibrillar protein isoforms is a major determinant of the contractile properties of skeletal muscle fibers. The diversity among isomyosins is related to the differences in the parameters of chemomechanical transduction as ATP hydrolysis rate and shortening velocity. Troponin and tropomyosin isoforms determine the variable sensitivity to calcium, whereas titin isoforms dictate the elastic properties of muscle fibers at rest. Both myosin and troponin isoforms contribute to the differences in the resistance to fatigue of muscle fibers.
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PMID:Molecular diversity of myofibrillar proteins: gene regulation and functional significance. 861 61

This article reports the research which led to the use of animal connective tissues in the construction of valvular prostheses and those which led to the use of electrically stimulated skeletal muscle for cardiac assistance. Although, very different at first glance these research have in common the transformation of biological tissues by physical or chemical means to adapt them to a new function. 1) Once implanted in a different species, animal connective tissues are destroyed by immunological reactions and collagen degeneration. These lesions can be prevented by both maskage of the antigenic groups and intermolecular crosslinking using Glutaraldehyde. The durability of such chemically treated tissues is based upon the stability of the biological material (concept of bioprosthesis) and not upon cell survival or tissue regeneration by host cell ingrowth (concept of graft). The valvular bioprostheses made from Glutaraldehyde treated pericardial tissue, keep after this treatment their advantage of biological tissues: they are not thrombogenic and do not require anticoagulation contrary to mechanical valves. Although they have a limited durability up to 10 to 15 years due to tissue calcification, they represent 40% of the valvular prostheses used in clinical practice today. 2) The clinical use of electrostimulated skeletal muscle has been delayed for a long time because of fatigue lesions. An original protocol of progressive sequential stimulation prior to the use of muscle prevents fatigue by the transformation of type I fatigable myosin into type II non fatigable myosin. The conditionned muscle i.e.: the latissimus dorsi, is then wrapped around the ventricles to either reinforce cardiac contraction or to replace a portion of the heart. In the past 10 years, this new operation of "dynamic cardiomyoplasty", has been performed in 84 patients suffering from the end stage heart failure in our institution and in over 500 patients throughout the world with significant functional improvement.
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PMID:[Induced tissue transformation and heart surgery]. 870 79

We studied changes in the mechanical properties and myosin isoform composition of rabbit tibialis anterior muscles that were subjected to continuous stimulation at 2.5 Hz for up to 12 wk. The effects of stimulation at 2.5 Hz were less profound than those observed for the same duration of stimulation at 10 Hz (12). Stimulation at 10 Hz for 12 wk induced complete transformation to a slow-contracting muscle homogeneous in slow myosin isoforms; stimulation for the same period at 2.5 Hz resulted in moderate changes in contractile speed and a very small increase in the synthesis of slow myosin isoforms. On the other hand, the fatigue resistance of muscles stimulated at 2.5 Hz was as great, in both isometric and dynamic fatigue tests, as that of the muscles stimulated at 10 Hz. Thus entire fast skeletal muscles can be transformed to a state in which fast myosin isoforms continue to be synthesized, but the oxidative capacity is sufficient to support sustained working at a higher power output than that associated with slow muscle.
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PMID:Induction of a fast-oxidative phenotype by chronic muscle stimulation: mechanical and biochemical studies. 877 58

We investigated the effects of clenbuterol on the muscle mass, contractile properties, myosin phenotype, and bioenergetic enzyme activity in the gastrocnemius (GS)-plantaris (PL)-soleus (SO) muscle complex. Rats were sham-injected or treated with clenbuterol (2 mg.kg-1, subcutaneously) for 14 d. Clenbuterol increased (P < 0.05) body weight and muscle complex weight. Also, clenbuterol treatment resulted in an increase in total muscle force production and maximal shortening velocity (P < 0.05). No difference (P > 0.05) in relative force production (force.g-1 muscle) existed between experimental groups. However, muscle fatigue increased with clenbuterol treatment. Myosin heavy chain (MHC) composition was not altered in the GS or PL muscles, but shifted toward the fast Type II MHC in the SO. Myosin light chain (MLC) composition was not altered in any of the muscles. Clenbuterol caused a decrease in oxidative and glycolytic enzyme activity in the GS and PL, but not the SO. These data suggest that the clenbuterol-induced increase in muscle mass and maximal force generation is due to hypertrophy of both fast and slow fibers. Furthermore, these findings support the notion that beta-agonists may be beneficial in combating conditions that result in muscle wasting and dysfunction.
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PMID:Effects of clenbuterol on contractile and biochemical properties of skeletal muscle. 878 54

1. The effect of muscle unit (MU) localization on physiological properties was investigated within the fast-twitch fatigue-resistant (FR) and fast-fatigable (FF) MU populations of rat medial gastrocnemius (MG) muscle. Single MG MUs were functionally isolated by microdissection of the ventral roots. FR and FF MU properties of the most proximal and distal muscle compartments were compared. The most proximal and distal compartment are subvolumes of the MG innervated by the most proximal and distal primary nerve branch, respectively. A subsample of the isolated units was glycogen depleted and muscle cross sections were stained for glycogen and myosin-adenosinetriphosphatase. 2. It was shown that proximal FF and FR units reached optimum length for force production at shorter muscle lengths compared with the distal FR and FF units. 3. The fast MUs of the proximal compartment had small territories that were located close to and/or within the mixed region (containing type I, IIA, IIX, and IIB fibers) of the muscle. The fast MUs of the distal compartment had greater territories that were located in the more superficial muscle part (containing only type IIX and IIB fibers) and in some cases spanned the entire area of the distal muscle compartment. 4. FR and FF MUs consisted of muscle fibers identified histochemically as type IIX and IIB, respectively. 5. Within each of the FR and FF MU populations, MUs that were located in the most proximal muscle compartment were more resistant to fatigue compared with the units located in the most distal compartment. 6. Cross-sectional fiber areas were smaller for the proximal FR and FF fibers, but specific force did not differ among units. Consequently, when account was taken of the innervation ratio, the proximal FR and FF units produced less force than distal units of the same type. Tetanic forces were 87 +/- 27 (SD) mN (proximal FR), 154 +/- 53 (SD) mN (distal FR), 142 +/- 25 (SD) mN (proximal FF), and 229 +/- 86 (SD) mN (distal FF). 7. The present findings suggest that with increasing demand placed on rat MG during in vivo locomotion, recruitment is likely to proceed from proximal to distal muscle parts within the FR and FF MU populations.
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PMID:Fast-twitch muscle unit properties in different rat medial gastrocnemius muscle compartments. 879 38

Motor units in cat diaphragm and tibialis posterior muscles were classified physiologically as slow-twitch, fast-twitch, fatigue-resistant, fast-twitch fatigue-intermediate, or fast-twitch fatigable. Motor unit fibers were then identified by glycogen depletion and classified as type I, IIa, IIb, or IIx on the basis of myofibrillar adenosinetriphosphatase-staining profiles and immunoreactivity for myosin heavy-chain (MHC) isoforms. In both muscles, slow-twitch and fast-twitch fatigue-resistant units comprised type I and IIa fibers expressing MHC-slow and MHC-2A isoforms, respectively. Fast-twitch fatigue-intermediate and fast-twitch fatigable units comprised type IIx fibers expressing the MHC-2X isoform. Some fast-twitch fatigue-intermediate units had a mixed composition with a few fibers (approximately 10%) expressing the MHC-2A isoform. Motor unit fiber succinate dehydrogenase (SDH) activity was quantified, and variability was estimated by the interquartile range, which was lower among motor unit fibers than in adjacent fibers of the same histochemical type but comparable to that along the length of individual fibers. We conclude that, despite the mixed-MHC phenotype of some diaphragm and tibialis posterior motor units, SDH activity is relatively uniform. This supports the hypothesis that motoneurons exert a predominant influence on muscle fiber SDH activity.
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PMID:Myosin phenotype and SDH enzyme variability among motor unit fibers. 880 28

Five goat latissimus dorsi muscles (LDM) were submitted to a progressive chronic electrostimulation program to reach an integrated understanding of the fast-to-slow transformation process in large mammals. LDM were regularly sampled and followed during a period of 8 months. Each sample was simultaneously assessed for histoenzymological study, myosin and LDH isoforms and bioenergetic capacities [NADH dehydrogenase cytochrome c oxidoreductase (NADH Cyt c OR), succinate dehydrogenase cytochrome c oxidoreductase (Succ Cyt c OR), cytochrome c oxidase (Cyt c Ox) and LDH]. Such muscles were also tested with and without completion of II to I transformation for their mechanical properties in isometric and isotonic strain gauge testing. The conversion of fast-to-slow myosin monitored by heavy chain (HC I) and light chain slow component (LC2s) began a few days after stimulation and was almost 100% after 100 days. The H-LDH isoforms evolved similarly but did not reach 100% conversion after 200 days. The activity of respiratory chain oxidases increased within 36 h but to a variable extent and peaked after 32 days, corresponding to a 75% transformation of myosin compared to initial levels. NADH Cyt c OR, Succ Cyt c OR, and Cyt c Ox, respectively increased 10-, 5- and 5-fold. These activities then significantly decreased before the completion of the myofibrillar transformation and reached a plateau with stable activities that remained 2- to 3-fold higher than the unstimulated LDM. LDH activity sharply decreased until day 62 (5-fold) and then plateaued. Functionally, muscle showed a reduced speed of contraction and moderate reduction in power output but had become fatigue-resistant. This study documents the transformation process in large mammals and suggests the dynamic relation between workload, aerobic-anaerobic metabolism and the contractile myofibrillar system.
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PMID:Type II to type I transformation of chronically stimulated goat latissimus dorsi muscle: a histoenzymological, biochemical, bioenergetic, and functional study. 883 65

Recent progress in defining molecular components of pathways controlling early stages of myogenesis has been substantial, but regulatory factors that govern the striking functional specialization of adult skeletal muscle fibers in vertebrate organisms have not yet been identified. A more detailed understanding of the temporal and spatial patterns by which specialized fiber characteristics arise may provide clues to the identity of the relevant regulatory factors. In this study, we used immunohistochemical, in situ hybridization, and Northern blot analyses to examine the time course and spatial characteristics of expression of myoglobin protein and mRNA during development of the distal hindlimb in the mouse. In adult animals, myoglobin is expressed selectively in oxidative, mitochondria-rich, fatigue-resistant myofibers, and it provides a convenient marker for this particular subset of specialized fibers. We observed only minimal expression of myoglobin in the hindlimb prior to the second day after birth, but a rapid and large (50-fold) induction of this gene in the ensuing neonatal period. Myoglobin expression was limited, however, to fibers located centrally within the limb which coexpress myosin isoforms characteristic of type I, IIA, and IIX fibers. This induction of myoglobin expression within the early postnatal period was accompanied by increased expression of nuclear genes encoding mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial protein expression that can be induced in adult muscle fibers by continuous motor nerve stimulation. This comparison suggests that progressive locomotor activity of neonatal animals may provide signals which trigger the development of the specialized features of oxidative, fatigue-resistant skeletal muscle fibers.
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PMID:Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb. 890 47

Developmental changes of muscle fibre composition in the various heads of the elbow, knee, and ankle extensors have been studied in three genera of cercopithecid monkeys. In order to circumvent the technical hindrances of usual histoenzymological procedures (fresh muscles need to be frozen at once at -80 degrees C), immunofluorescence methods were used and technical adjustments were successfully carried out to make the study of formaldehyde-preserved muscles possible. Clear responses to antibodies against adult fast myosin in newborn macaques demonstrated that, at birth, adult myosins have already replaced the fetal isoforms, thus providing a reliable marker for the study of postnatal evolution of the muscle fibre composition. For each one of the three joints, from birth to adulthood, the percentage of slow, fatigue-resistant fibres increases only in that head of the extensor muscle groups which is specialized in maintaining posture by counteracting gravity (the 'postural' head). Hence, the question is raised of the relationships between such cytological evolution, developmental changes in postural behaviour, and body weight increase.
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PMID:Developmental changes in the fibre composition of elbow, knee, and ankle extensor muscles in cercopithecid monkeys. 895 50

During fatigue, muscles become weaker, slower, and more economical at producing tension. Studies of skinned muscle fibers can explain some but not all of these effects, and, in particular, they are less economical in conditions that simulate fatigue. We investigated three factors that may contribute to the different behavior of skinned fibers. 1) Skinned fibers have increased myofilament lattice spacing, which is reversible by osmotic compression. 2) A myosin subunit becomes phosphorylated during fatigue. 3) Inosine 5'-monophosphate (IMP) accumulates during fatigue. We tested the response of phosphorylated and unphosphorylated single skinned fibers (isometric tension, contraction velocity, and adenosinetriphosphatase activity) to changes in lattice spacing (0-5% dextran) and IMP (0-5 mM) in the presence of altered concentrations of P(i) (3-25 mM), H+ (pH 7-6.2), and ADP (0-5 mM). The response of maximally activated skinned fibers to the direct metabolites of ATP hydrolysis is not altered by osmotic compression, phosphorylating myosin subunits, or increasing IMP concentration. These factors, therefore, do not explain the discrepancy between intact and skinned fibers during fatigue.
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PMID:Response of compressed skinned skeletal muscle fibers to conditions that simulate fatigue. 910 68


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