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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.
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PMID:Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release. 689 25

Three experiments were carried out with male broiler chickens reared from day- old to 6 weeks of age on semi-purified diets containing 10% fresh (Expt. 1 and 3) or oxidized (Expt. 2) re-esterified triglycerides with a fatty acid composition similar to that of soya bean oil containing increasing concentrations of either a mixture of d-alpha-, gamma-, delta-tocopherylacetate (d-tocopherols) of natural source or dl-alpha- tocopheryl acetate (dl-tocopherol). In Expt. 1 and 2 the mixture of d-tocopherols consisted of 35.7% d-alpha-, 45.3% d-gamma- and 19.0% d-delta-, while in Expt. 3 the distribution was 25.3% d-alpha-, 28.1% d-gamma- and 10.8% d-gamma- in 35.8% re-esterified triglycerides. The relative biopotency of d-alpha-: gamma-: delta-tocopherol was anticipated to be 100:25:1, whereas that of dl-alpha-tocopherol was 74% relative to d-alpha-tocopherol. The experiments demonstrate that the results obtained for the biological activity depend on the response parameters chosen. With respect to gain in weight, feed conversion, relative organ weight, packed cell volume (PCV), ELP (erythrocyte lipid peroxidation), plasma activities of glutamate-oxaloacetate-transaminase (GOT), creatine kinase (CK) and glutathione peroxidase (GSH-Px) and plasma Na+ concentration, the mixture of natural source tocopherols was identical to that of dl-alpha-tocopheryl acetate, although the concentration of alpha-tocopherol was only about one third of that of dl-alpha-tocopherol. Differences between natural source and synthetic tocopherols were expectedly observed with respect to plasma concentrations of alpha-, gamma-, delta-tocopherol. Differences between the two forms as to muscular dystrophy, in vitro haemolysis and potassium concentration in plasma were ambiguous. It is suggested that the function of d-alpha-, gamma-, delta-tocopherol in erythrocyte fragility and skeletal muscle structure should be compared to that of dl-alpha-tocopherol in future investigations.
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PMID:The biological activity of natural source tocopherols in chickens fed fresh or oxidized fat rich in linoleic acid. 821 3

Modern molecular biology has revealed vast numbers of large and complex proteins and genes that regulate body function. By contrast, discoveries over the past ten years indicate that crucial features of neuronal communication, blood vessel modulation and immune response are mediated by a remarkably simple chemical, nitric oxide (NO). Endogenous NO is generated from arginine by a family of three distinct calmodulin- dependent NO synthase (NOS) enzymes. NOS from endothelial cells (eNOS) and neurons (nNOS) are both constitutively expressed enzymes, whose activities are stimulated by increases in intracellular calcium. Immune functions for NO are mediated by a calcium-independent inducible NOS (iNOS). Expression of iNOS protein requires transcriptional activation, which is mediated by specific combinations of cytokines. All three NOS use NADPH as an electron donor and employ five enzyme cofactors to catalyze a five-electron oxidation of arginine to NO with stoichiometric formation of citrulline. The highest levels of NO throughout the body are found in neurons, where NO functions as a unique messenger molecule. In the autonomic nervous system NO functions NO functions as a major non-adrenergic non-cholinergic (NANC) neurotransmitter. This NANC pathway plays a particularly important role in producing relaxation of smooth muscle in the cerebral circulation and the gastrointestinal, urogenital and respiratory tracts. Dysregulation of NOS activity in autonomic nerves plays a major role in diverse pathophysiological conditions including migraine headache, hypertrophic pyloric stenosis and male impotence. In the brain, NO functions as a neuromodulator and appears to mediate aspects of learning and memory. Although endogenous NO was originally appreciated as a mediator of smooth muscle relaxation, NO also plays a major role in skeletal muscle. Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS occurs at the plasma membrane of skeletal muscle which facilitates diffusion of NO to the vasculature to regulate muscle perfusion. nNOS protein occurs in the dystrophin complex in skeletal muscle and NO may therefore participate in the pathophysiology of muscular dystrophy. NO signalling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signalling is largely regulated at the level of NO biosynthesis. Acute control of nNOS activity is mediated by allosteric enzyme regulation, by posttranslational modification and by subcellular targeting of the enzyme. nNOS protein levels are also dynamically regulated by changes in gene transcription, and this affords long-lasting changes in tissue NO levels. While NO normally functions as a physiological neuronal mediator, excess production of NO mediates brain injury. Overactivation of glutamate receptors associated with cerebral ischemia and other excitotoxic processes results in massive release of NO. As a free radical, NO is inherently reactive and mediates cellular toxicity by damaging critical metabolic enzymes and by reacting with superoxide to form an even more potent oxidant, peroxynitrite. Through these mechanisms, NO appears to play a major role in the pathophysiology of stroke, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
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PMID:Endogenous nitric oxide synthesis: biological functions and pathophysiology. 1063 Jun 82