cyclic-gmp and Muscular-Dystrophy--Animal

Topics: Aerobiosis; Aging; Anaerobiosis; Animals; Calcium; Cyclic AMP; Cyclic GMP; Fasting; Glucose-6-Phosphate; Glucosephosphates; Hormones; Islets of Langerhans; Kinetics; Lysophosphatidylcholines; Mice; Muscles; Muscular Dystrophy, Animal; Phospholipases A; Rats; Skin

Muscular dystrophies are characterized by primary wasting of skeletal muscle for which no satisfactory therapy is available. Studies in animal models have shown that stem cell-based therapies may improve the outcome of the disease, and that mesoangioblasts are promising stem cells in this respect. The efficacy of mesoangioblasts in yielding extensive muscle repair is, however, still limited. We found that mesoangioblasts treated with nitric oxide (NO) donors and injected intra-arterially in alpha-sarcoglycan-null dystrophic mice have a significantly enhanced ability to migrate to dystrophic muscles, to resist their apoptogenic environment and engraft into them, yielding a significant recovery of alpha-sarcolgycan expression. In vitro NO-treated mesoangioblasts displayed an enhanced chemotactic response to myotubes, cytokines and growth factors generated by the dystrophic muscle. In addition, they displayed an increased ability to fuse with myotubes and differentiating myoblasts and to survive when exposed to cytotoxic stimuli similar to those present in the dystrophic muscle. All the effects of NO were cyclic GMP-dependent since they were mimicked by treatment with the membrane permeant cyclic-GMP analogue 8-bromo-cGMP and prevented by inhibiting guanylate cyclase. We conclude that NO donors exert multiple beneficial effects on mesoangioblasts that may be used to increase their efficacy in cell therapy of muscular dystrophies.

Topics: Animals; Apoptosis; Cell Differentiation; Cell Movement; Cells, Cultured; Cyclic GMP; Gene Expression Profiling; Immunohistochemistry; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Muscle, Smooth, Vascular; Muscular Dystrophy, Animal; Nitric Oxide Donors; Sarcoglycans; Stem Cell Transplantation; Stem Cells

Topics: Amino Acids; Animals; Cyclic GMP; Dark Adaptation; Haplorhini; Histological Techniques; Mice; Mice, Mutant Strains; Muscular Dystrophy, Animal; Photoreceptor Cells; Retina; Taurine; Tissue Distribution; Turtles

cAMP and cGMP contents were determined in the skeletal and cardiac muscle of normal and dystrophic mice. cAMP content increased in the dystrophic muscle at every stage of the disease whereas cGMP content decreased in the preliminary stages and increased at the terminal stage of the disease. The content of both nucleotides per heart was not affected in murine dystrophy. Thus, levels of cyclic nucleotides appear to be selectively altered in dystrophic skeletal muscle.

Topics: Animals; Cyclic AMP; Cyclic GMP; Mice; Muscles; Muscular Dystrophy, Animal; Myocardium

Cyclic AMP and cyclic GMP phosphodiesterase activity was determined in the heart and in nine skeletal muscles of control and dystrophic Re 129/J male and female mice. Phosphodiesterase activity in the presence of 0.5 mM cyclic AMP of cyclic GMP was increased in all the muscle but the heart of dystrophic mice.

Topics: Animals; Cyclic AMP; Cyclic GMP; Female; Male; Mice; Muscles; Muscular Dystrophy, Animal; Myocardium; Phosphoric Diester Hydrolases

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Alanine; Amino Acids; Animals; Bucladesine; Cyclic AMP; Cyclic GMP; Epinephrine; Glutamine; Mice; Muscle Proteins; Muscles; Muscular Dystrophy, Animal; Phosphorylases; Serotonin; Species Specificity

The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages.

Topics: Animals; Chick Embryo; Cyclic AMP; Cyclic GMP; Humans; Mice; Muscles; Muscular Dystrophies; Muscular Dystrophy, Animal; Radioimmunoassay

A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.

Topics: Allosteric Regulation; Animals; Cyclic AMP; Cyclic GMP; Glucosephosphates; Glycolysis; Mice; Muscles; Muscular Dystrophy, Animal; Phosphofructokinase-1

Adenyl cyclase and cyclic nucleotide phosphodiesterase activities were assayed in homogenates of hind leg skeletal muscle from dystrophic and normal mice. Adenyl cyclase activity was stimulated 2.5 times by epinephrine and 6 times by fluoride over the basal activity in both dystrophic and normal mice. The activity of adenyl cyclase from dystrophic muscle of mice was significantly higher than that of normal mice under all the conditions tested (i.e. basal, epinephrine and fluoride). Cyclic nucleotide phosphodiesterase from skeletal muscle of mice has two Km's (2.1 and 11 mumol/l) which suggests the existence of either two forms of enzyme or a single enzyme with negative cooperativity. The activity of this enzyme was significantly elevated in the skeletal muscle of dystrophic mice compared to the normal controls. The available evidence suggests that the same cyclic nucleotide phosphodiesterase is responsible for the hydrolysis of both cyclic AMP and cyclic GMP.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Animals; Cyclic GMP; Kinetics; Mice; Muscles; Muscular Dystrophy, Animal; Phosphoric Diester Hydrolases; Subcellular Fractions