Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticosteroids have been shown to produce a myopathy of peripheral skeletal muscle, characterized predominantly by Type II fiber atrophy. To determine if similar histologic and histochemical changes occur in the diaphragm and whether the in vitro contractile properties of this muscle are adversely affected by steroids, we studied two groups of hamsters. The experimental group received triamcinolone while a control group received saline, both given daily for 3 wk as i.m. injections. Soleus (Sol) and extensor digitorum longus (EDL) muscles and costal diaphragm muscle sections were stained for histologic (hematoxylin and eosin, modified Gomori trichrome) and histochemical (myosin ATPase, succinate dehydrogenase [SDH]) analysis. Muscle fiber proportions and cross-sectional areas (CSA) were measured from myosin ATPase sections. In vitro studies of isometric contractions were carried out on small strips of costal diaphragm, measuring maximal isometric twitch (Pt) and tetanus (Po) tensions, time to peak tension (TTP), half relaxation time (1/2 RT), force-frequency relationship, and fatigue characteristics (60 Hz tetani; duty cycle, 0.5). Triamcinolone treatment resulted in no change in muscle fiber proportions. There was no effect on Type I fiber CSA; however, there was Type IIa (Sol, EDL) and Type IIb (diaphragm, EDL) fiber atrophy in triamcinolone-treated animals. Pt and Po (normalized for weight) of diaphragm strips were not different. There was a prolongation in TTP and 1/2 RT, a left shift in the force-frequency curve, and a reduced fatiguability of triamcinolone-treated diaphragm (P less than 0.05). We conclude that a steroid myopathy could be explained by a loss of muscle mass (Type IIb fiber atrophy) rather than an intrinsic impairment in contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1989 Sep
PMID:Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle. 262 59

A 37-year-old man suffered from photosensitivity and urinary casts with serological findings of positive anti-DNA antibody, LE cells and false positive VD reaction in September of 1979. He developed general fatigue, dyspnea and diplopia with ptosis of bilateral eyelids in November of 1979, which were improved by the anti-cholinesterase drugs. In January of 1980, he had an attack of unconsciousness and his chest X-ray film showed several tumorous shadows in the anterior mediastinum and middle and lower lung fields. Treating him with chemotherapy of VEMP, the pulmonary shadows disappeared. However, he developed severe muscle weakness with an elevated CPK (430 mU/ml) and a myogenic EMG pattern along with an increased anti-acetylcholine receptor antibody (243 n Mol/l), dysphagia and eyelid-ptosis. He died in September of 1985 and his autopsy disclosed a malignant thymoma of mixed type in the anterior mediastinum and an atrophy and fibrosis with infiltration of inflammatory cells in the striated muscles.
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PMID:[An autopsy case of a patient with myasthenia gravis who showed various symptoms of collagen diseases and complicated with malignant thymoma]. 281 7

The effect of fatigue (running to exhaustion) on the Vmax activity of the key glycolytic enzymes measured at saturating substrate concentrations in muscles, liver and brain of sedentary and trained (running on a treadmill one h/day at 20 m/min, five days/week for six months) female Zucker fatty rats and their lean littermates was investigated. In the sedentary rats, fatigue increased the activity of phosphofructokinase (PFK) in the red vastus muscle by 82% in lean, and 120% in obese rats. In the trained rats, fatigue increased PFK activity by 28% in the white vastus muscle of lean rats. In the lean animals, hexokinase (HK) activity was decreased by 26% in the red vastus of sedentary rats, and by 29% in the white vastus of trained rats upon fatiguing. Pyruvate kinase (PK) activity was also decreased by 29% in the white vastus of fatigued lean animals. Training by itself had no effect on the activity of glycolytic enzymes, except PK activity which was increased by 27% in the cortex of the lean animals. It is concluded that in the Zucker rat, these glycolytic enzymes may play a differential role in regulating glycolysis during exercise and fatigue; the extent of their involvement differs depending upon the type of tissue studied and exercise. In view of the reported short half-life (7-17 h) of PFK and its covalent modification, it is suggested that the total content and/or phosphorylation status of the enzyme may be affected in animals subjected to long-term fatigue.
Mol Cell Biochem 1988 Jun
PMID:Effect of exercise on glycolytic enzymes of Zucker fatty rats. 297 74

The purpose of this study was to examine the Ca2+-Mg2+ myofibrillar ATPase and protein composition of cardiac and skeletal muscle following strenuous activity to voluntary exhaustion. Sprague-Dawley rats (200 g) were assigned to a control and exercised group, with the run group completing 25 m.min-1 and 8% grade for 1 hour. Following activity, the myocardial Ca2+-Mg2+ myofibrillar ATPase activity -pCa relationship had undergone a rightward shift in the curve. Electrophoretic analysis revealed a change in the pattern of cardiac myofibrillar protein bands, particularly in the 38-42 Kdalton region. Enzymatic analysis of myofibrillar proteins from plantaris muscle, revealed no change in Ca2+ regulation following exercise. Electronmicrographic and electrophoretic analysis revealed extensively disrupted sarcomeric structure and a change in the ratio of several plantaris myofibrillar proteins. No difference was observed for myosin: Actin: tropomyosin ratios; however a dramatic reduction in 58 and 95 Kdalton proteins were evident. The results indicate that prolonged running is associated with similar responses in cardiac and skeletal muscle myofibrillar protein compositions. The abnormalities in myofibrillar ultrastructure may implicate force transmission failure as a factor in exercised-induced muscle damage and/or fatigue.
Mol Cell Biochem 1988 Sep
PMID:Influence of exercise on cardiac and skeletal muscle myofibrillar proteins. 297 50

Daily administration of dithiobiuret (DTB, 1 mg/kg X 6 days, ip) produced delayed onset muscle weakness in rats as indicated by failure in a treadmill test. In nerve-muscle preparations from DTB-intoxicated rats neuromuscular toxicity was manifested as contractile fatigue during tetanic nerve stimulation. As muscle weakness developed, feed intake decreased and the animals lost body weight. Water intake was not altered during this time, but urine output was increased concomitant with the development of muscle weakness and resulted in a state of negative water balance. Daily administration of d-penicillamine (d-PEN) antagonized DTB-induced treadmill failure in a dose-dependent fashion. A daily dose of d-PEN (1 mMol/kg, ip) that completely antagonized treadmill failure also antagonized the contractile fatigue, reduced feed intake, weight loss and negative water balance caused by DTB administration. In rats already intoxicated with DTB, initiating daily d-PEN treatment or discontinuing further DTB administration, caused the animals to recover normal treadmill performance after a latent period of five days. A single dose of d-PEN (1 mMol/kg, iv) was not effective in reversing treadmill failure or contractile fatigue in rats already intoxicated with DTB. Thus, continuous daily administration of d-PEN was necessary for it to be effective. A single dose of d-PEN (1 m Mol/kg, ip) administered one hr after [14C]-DTB (1 mg/kg, ip) did not affect the plasma and tissue concentrations of DTB-derived radioactivity or their corresponding elimination kinetics. Cumulative urinary and fecal excretion of DTB-derived radioactivity were also unaffected by d-PEN administration as were the relative proportions of DTB and two of its metabolites, monothiobiuret and thiuret, in urine. Other agents that produced dose-dependent antagonism of DTB toxicity were diethyldithiocarbamate, disulfiram, cysteamine and 2,2'-dipyridyl. Considering the chemical and biological properties of DTB and its antagonists, a mechanism of antagonism involving an alteration of the thiol-disulfide and/or divalent metal cation status of motor axon terminals is postulated.
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PMID:Antagonism of dithiobiuret toxicity in rats. 301 25

A clinical phase I trial with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was performed in 30 patients with advanced malignancies. The maximal tolerated dose (MTD) by 3 times weekly intramuscular (i.m.) application was 150 micrograms m-2. Main subjective toxicities including chills, fever, hypotension, fatigue, and anorexia were dose-related. In addition, transient changes in hematologic parameters and lipid metabolism were noted. Two out of 25 evaluated patients showed a minor tumor response after eight weeks of therapy. There was evidence for an improvement of in vivo immuneresponsiveness as revealed from positive delayed type hypersensitivity (DTH) skin tests of 3 out of 6 pretherapeutically anergic patients. We conclude from this phase I trial that rTNF-alpha can be safely administered at doses up to 150 micrograms m-2 i.m., 3 times weekly, without evidence of cumulative toxicity in long-term treatment.
Mol Biother 1988
PMID:Phase I study of recombinant human tumor necrosis factor-alpha in patients with advanced malignancies. 326 69

Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.
Mol Pharmacol 1988 Feb
PMID:Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle. 334 81

The characteristics of long-duration inhibitory postsynaptic potentials (1-IPSPs) which are evoked in rat frontal neocortical neurons by local electrical stimulation were investigated with intracellular recordings from an in vitro slice preparation. Stimulation with suprathreshold intensities evoked 1-IPSPs with typical durations of 600-900 msec at resting membrane potential. Conductance increases of 15-60% were measured at the peak amplitude of 1-IPSPs (150-250 msec poststimulus). The duration of the conductance increases during 1-IPSPs displayed a significant voltage dependence, decreasing as the membrane potential was depolarized and increasing with hyperpolarization. The reversal potential of 1-IPSPs is significantly altered by reductions in the extracellular potassium concentration. Therefore it is concluded that 1-IPSPs in rat neocortical neurons are generated by the activation of a potassium conductance. 1-IPSPs exhibit stimulation fatigue. Stimulation with a frequency of 1 Hz produces a complete fatigue of the conductance increases during 1-IPSPs after approximately 20 consecutive stimuli. Recovery from this fatigue requires minutes. 1-IPSPs are not blocked by bicuculline but are blocked by baclofen.
Cell Mol Neurobiol 1987 Mar
PMID:Characteristics of long-duration inhibitory postsynaptic potentials in rat neocortical neurons in vitro. 359 15

Rat myofibers in the resting state and under imposed conditions of moderate to severe physiological, pharmacological, and mechanical stress were prepared by ultrarapid freezing and examined by freeze fracture. In rapidly frozen rat myofibers, caveolae morphology and distribution were found to be unchanged by brief or prolonged rest, brief direct electrical stimulation and concomitant contractile activity, prolonged direct electrical stimulation (to fatigue), myofiber stretch (within normal myofiber limits), or careful compressive scission. However, caveolae were greatly reduced or eliminated in number and size by severe mechanical disruption (shredding and/or tearing) of myofibers. Thus, we conclude that unlike apparently similar surface specialization in other cell types, skeletal muscle caveolae are not transient stages in a caveolae----vesicle endocytotic-exocytotic cycle, nor are they a membrane reservoir for normal stretch/contractile activity. Rather, they are (semi)permanent structures in the muscle plasma membrane with as yet undetermined function and kinetics.
J Ultrastruct Mol Struct Res
PMID:Ultrarapid freezing reveals that skeletal muscle caveolae are semipermanent structures. 368 Oct 18

Our previous work showed that myosin phosphorylation decreased the ATPase activity of skeletal muscle myofibrils that were lightly fixed with glutaraldehyde. The fixation process prevented sarcomere shortening and destruction of the ordered filament array upon the addition of ATP. We have now extended these results to myofibrils prepared from hearts of rabbits, dogs and rats. Myofibrils were phosphorylated by incubation with myosin light chain kinase, calmodulin and either ATP-gamma s or ATP, for 15 minutes at 25 degrees C. The extent of myosin light chain phosphorylation was 50% to 80%. The ATPase activity of unphosphorylated myofibrils was not altered by reaction with 0.01% glutaraldehyde for 5 minutes at 0 degrees C, and the ATPase activity of unfixed myofibrils was not changed by phosphorylation. However, phosphorylation decreased the ATPase activity of fixed myofibrils by 50%. The effect on myocardial myofibrillar ATPase activity of phosphorylation was similar in the three animal species. These results suggest that in both skeletal and cardiac muscle, myosin phosphorylation decreases the rate of cross-bridge cycling resulting in decreased energy expenditure. It also appears that the effect of myosin light chain phosphorylation on ATPase activity requires an ordered myofilament structure.
J Mol Cell Cardiol 1984 Jul
PMID:Myosin phosphorylation decreases the ATPase activity of cardiac myofibrils. 623


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