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

The aim of the present study was to further subdivide the type II fibers of the human thyroarytenoid and posterior cricoarytenoid muscles by means of a modified myosin ATPase reaction. In order to understand the functioning of these highly strained muscles better, it is important to know the respective percentage of fatigue-resistant type IIA fibers and fatigable type IIB fibers. The material comprised the larynges of seven laryngectomized males aged between 45 and 70 years and four laryngectomized females aged between 39 and 72 years. After having been frozen in nitrogen, 10-microns-thick sections were cut from the laryngeal muscles in a cryostat. The pH-lability of the enzyme that can be utilized in a classical myosin ATPase reaction permits a differentiation between fiber types I, IIA and IIB. Evidently, this is not possible with every human muscle. The fiber types IIA and IIB of the thyroarytenoid and the posterior cricoarytenoid muscles could be clearly distinguished by means of the inhibition reactivation myofibrillar ATPase technique. Using this method, the myosin ATPase enzyme was initially inhibited by hydroxymercuribenzoate and subsequently reactivated by cysteine. Regarding the incidence of type I and IIA fibers, there was a statistically significant difference between the thyroarytenoid and the posterior cricoarytenoid muscles. The type IIA fiber content was statistically significantly higher in the arytenoid muscle than in the posterior cricoarytenoid muscle. The percentage of type IIB fibers was low, not only in the thyroarytenoid muscle and the posterior cricoarytenoid muscle but also in the other laryngeal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fiber differentiation of the human laryngeal muscles using the inhibition reactivation myofibrillar ATPase technique. 141 83

The gamma-crystallin fractions II, III and IV from calf eye lens were treated with the thiol-specific fluorescent probe 2-(4'-maleimidylanilino)naphthalene-6-sulfonate (MIANS), in order to determine the reactivity of the seven (gamma-II) or six (gamma-III, gamma-IV) cysteine residues. Two classes of reactive cysteines were distinguished by variations in fluorescence intensity with increasing molar excess of the probe, and approximately three cysteines were nonreactive in each gamma-crystallin. From the position of the emission maximum, it is apparent that MIANS-labeled cysteines of gamma-IV are in the least hydrophobic environment. Fluorescence energy transfer was observed from tryptophan to MIANS-labeled cysteines in both gamma-II and gamma-III crystallins, with efficiencies of 86% and 89%, respectively, but not in gamma-IV crystallin. We suggest that the spatial arrangements and microenvironments of cysteine residues of gamma-crystallins are sufficiently different from each other to account for the variations in fluorescence characteristics of the MIANS-labeled proteins and the lack of energy transfer in gamma-IV crystallins.
 ...
PMID:Structure and stability of gamma-crystallins. II. Differences in microenvironments and spatial arrangements of cysteine residues. 381 5

The cytoskeleton plays a pivotal role in lectin-induced lymphocyte blastogenesis. Microtubule disrupting agents, many of which are sulfhydryl (SH) reagents, interfere with cytoskeletal-dependent cell functions including lymphocyte blastogenesis and agglutination. For example, hydroquinone (HQ) and N-ethylmaleimide (NEM) inhibit lectin-stimulated lymphocyte blastogenesis and agglutination at concentrations (10(-5)M) that do not reduce cell viability or ATP production. Indicative of the SH-specificity of these effects, only L-cysteine protects against HQ or NEM inhibition of blastogenesis and agglutination. Other compounds, including L-serine, DL-lysine and imidazole, have no protective effect. These and other findings previously reported suggest a selective interaction of HQ, or its oxidation product, p-benzoquinone (p-BQ) with SH groups critical to early G1 events associated with lymphocyte activation. These compounds show similar SH specificity in inhibiting microtubule assembly in vitro. The subcellular target specificity (cytoskeleton) exhibited by these compounds was compared to that of Adriamycin (ADR), a complex polycyclic quinone with known immunotoxic activity. ADR inhibited microtubule assembly in vitro and inhibited lymphocyte blastogenesis, however, these effects were not correlated with a loss of agglutination nor was toxicity protected against by the addition of SH compounds. The combination of cell culture methods together with application of techniques to measure microtubule assembly in vitro provides an effective means to discriminate between agents that selectively interfere with cytoskeletal-dependent function and those producing non-specific effects associated with cell death, such as decreased energy production or increased membrane permeability.
 ...
PMID:Alteration of lymphocyte function by quinones through a sulfhydryl-dependent disruption of microtubule assembly. 665 42

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.
 ...
PMID:N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro. 796 Dec 53

The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between the immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.
 ...
PMID:Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. 936 43

Abnormally low plasma cystine levels have been found in the late asymptomatic stage of HIV infection and several other diseases associated with progressive loss of skeletal muscle mass. The phenomenon is commonly associated with a low NK cell activity, skeletal muscle wasting or muscle fatigue and increased rates of urea production. In its extreme form, the negative nitrogen balance leads to overt cachexia and is associated with severe debilitation and psychological stress. The low NK cell activity is in most cases not life-threatening but may be disasterous in HIV infection, because it may compromise the initially stable balance between immune system and virus and trigger disease progression. This review summarizes briefly (i) the role of cysteine in the physiological regulation of body cell mass and the development of skeletal muscle wasting, and (ii) the role of glutathione in the immune system.
 ...
PMID:Role of cysteine and glutathione in signal transduction, immunopathology and cachexia. 969 16

Oxidative stress contributes to muscular fatigue. GSH is the major intracellular antioxidant, the biosynthesis of which is dependent on cysteine availability. We hypothesized that supplementation with a whey-based cysteine donor [Immunocal (HMS90)] designed to augment intracellular GSH would enhance performance. Twenty healthy young adults (10 men, 10 women) were studied presupplementation and 3 mo postsupplementation with either Immunocal (20 g/day) or casein placebo. Muscular performance was assessed by whole leg isokinetic cycle testing, measuring peak power and 30-s work capacity. Lymphocyte GSH was used as a marker of tissue GSH. There were no baseline differences (age, ht, wt, %ideal wt, peak power, 30-s work capacity). Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both peak power [13 +/- 3.5 (SE) %, P < 0.02] and 30-s work capacity (13 +/- 3.7%, P < 0.03) increased significantly in the Immunocal group, with no change (2 +/- 9.0 and 1 +/- 9.3%) in the placebo group. Lymphocyte GSH also increased significantly in the Immunocal group (35.5 +/- 11.04%, P < 0.02), with no change in the placebo group (-0.9 +/- 9.6%). This is the first study to demonstrate that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance.
 ...
PMID:Effect of supplementation with a cysteine donor on muscular performance. 1051 67

Zinc is involved in the biochemical processes supporting life, such as cellular respiration, DNA reproduction, maintenance of cell membrane integrity and free radical scavenging. Zinc is required for the activity of more than 300 enzymes, covering all 6 classes of enzyme activity. Zinc binding sites in proteins are often of distorted tetrahedral or trigonal bipyramidal geometry, made up of the sulphur of cysteine, the nitrogen of histidine or the oxygen of aspartate and glutamate, or a combination. Zinc in proteins can either participate directly in chemical catalysis or be important for maintaining protein structure and stability. The nutritional habits of elite athletes during training and competition are quite different from the recommended diet in the majority of the population. Endurance athletes often adopt an unusual diet in an attempt to enhance performance: an excessive increase in carbohydrates and low intake of proteins and fat may lead to suboptimal zinc intake in 90% of athletes. Mild zinc deficiency is difficult to detect because of the lack of definitive indicators of zinc status. In athletes, zinc deficiency can lead to anorexia, significant loss in bodyweight, latent fatigue with decreased endurance and a risk of osteoporosis.
 ...
PMID:Zinc status in athletes: relation to diet and exercise. 1147 19

Exercise generates free radicals only when it is exhaustive. Free radicals are involved in tissue damage caused by exercise. Antioxidant vitamins (vitamin C and E) and other antioxidants such as coenzyme Q, and N-acetyl cysteine prevent muscle damage and decrease muscle fatigue. The main aim of this paper was to test the possible protective effect of two new antioxidants, cyanoside chloride and chromocarbe diethylamine, on the oxidative stress generated by exhaustive exercise. The antioxidants were given to rats daily (50 mg/kg) in drinking water for 30 days. Blood oxidized glutathione/ reduced glutathione ratio, and plasma malondialdehyde levels were determined as indexes of oxidative stress. Plasma creatine kinase, alanine-aminotransferase and lactate dehydrogenase activities were used as markers of muscle damage. Both cyanoside chloride and chromocarbe diethylamine were more effective than vitamin C in the prevention of glutathione oxidation in blood. Furthermore, cyanoside chloride and chromocarbe diethylamine partially prevented muscle damage. Chromocarbe diethylamine was the most effective compound in the prevention of exercise-induced lipid peroxidation (malondialdehyde) in plasma.
 ...
PMID:Cyanoside chloride and chromocarbe diethylamine are more effective than vitamin C against exercise-induced oxidative stress. 1188 79

Amyloid beta-peptide [Abeta(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Abeta(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, Abeta induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). These alkenals covalently bind to synaptosomal protein cysteine, histidine, and lysine residues by Michael addition to change protein conformation and function. HNE or acrolein binding to proteins introduces a carbonyl to the protein, making the protein oxidatively modified as a consequence of lipid peroxidation. Immunoprecipitation of proteins from AD and control brain, obtained no longer than 4h PMI, showed selective proteins are oxidatively modified in the AD brain. Creatine kinase (CK) and beta-actin have increased carbonyl groups, and Glt-1, a glutamate transporter, has increased binding of HNE in AD. Abeta(1-42) addition to synaptosomes also results in HNE binding to Glt-1, thereby coupling increased Abeta(1-42) in AD brain to increased lipid peroxidation and its sequelae and possibly explaining the mechanism of glutamate transport inhibition known in AD brain. Abeta also inhibits CK. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. The epsilon-4 allele of the lipid carrier protein apolipoprotein E (APOE) allele is a risk factor for AD. Synaptosomes from APOE knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. Further, synaptosomes from allele-specific APOE knock-in mice have tiered vulnerability to Abeta(1-42)-induced oxidative stress, with APOE4 more vulnerable to Abeta(1-42) than are those from APOE2 or APOE3 mice. These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by Abeta(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE allele-related risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress in AD neurodegeneration.
 ...
PMID:Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. 1239 66


1 2 3 4 Next >>