Biochemical changes in progressive muscular dystrophy. XI. Cyclic nucleotides in the skeletal and cardiac muscle of normal and dystrophic mice

Srivastava, Uma; Sebag, Mikael; Thakur, M.L.

doi:10.1139/y81-051

Cited by 4 publications

(1 citation statement)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed in skeletal muscle cells, glycogenin mRNA expression was inhibited with increasing concentrations of cAMP [30]. It has been demonstrated previously that cAMP levels are increased in muscles from mdx mice [31], which would support the reduction in glycogenin mRNA expression observed in dystrophic muscle (Fig. 2E).…”

Section: Discussionsupporting

confidence: 81%

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

et al. 2014

View full text Add to dashboard Cite

BackgroundDuchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice.ResultsDystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype.ConclusionWe identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen.

show abstract

Section: Discussionsupporting

confidence: 81%

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

Phosphodiesterases S-sulfhydration contributes to human skeletal muscle function.

Vellecco

Panza

Bibli

et al. 2022

Pharmacological Research

View full text Add to dashboard Cite

Biochemical changes in progressive muscular dystrophy. XII. Cyclic nucleotides in lymphoid and nonlymphoid organs of dystrophic mice

Thakur¹,

Sebag²,

Srivastava³

1986

Biochem. Cell Biol.

View full text Add to dashboard Cite

Concentrations of cAMP and cGMP were measured (per milligram DNA) in the lymphoid (thymus, spleen) and nonlymphoid organs (liver, brain, kidney, lungs, heart, pancreas, skeletal muscle, lens) of normal (+/+) and dystrophic (dy/dy) 129 ReJ mice aged 30, 60, and 90 days. The cAMP concentrations in the thymus did not reveal any significant differences at 30 and 60 days of dystrophy, but were considerably higher (2-fold) at 90 days. cGMP concentrations were decreased in the thymus at 30 days (0.20-fold) and markedly elevated at 60 (2-fold) and 90 days (3-fold) of the disease. The [cAMP]/[cGMP] ratio was increased (1.30-fold) at 30 days of dystrophy, and this was followed by a sharp decline at 60 days (2-fold), with a lesser decrease at 90 days (0.34-fold). In the spleen, the cAMP concentrations were augmented significantly in all stages of dystrophy (1.5- to 2.6-fold). cGMP (per milligram DNA) did not show any significant variation at 30 and 60 days of the disease but was increased (3-fold) at 90 days. The [cAMP]/[cGMP] ratio, which was enhanced in the spleen at 30 (2-fold) and 60 days (1.5-fold), demonstrated no change at 90 days of dystrophy. These results indicated significant differences in the concentration of cyclic nucleotides and their ratios in the thymus and spleen of 129 ReJ dy/dy mice. The modifications were not limited to lymphoid organs alone, having been noted in the nonlymphoid organs as well. These changes could, in turn, influence immune responsiveness and could cause immunodepression in dystrophic mice.

show abstract

Biochemical changes in progressive muscular dystrophy. XI. Cyclic nucleotides in the skeletal and cardiac muscle of normal and dystrophic mice

Cited by 4 publications

References 2 publications

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

Phosphodiesterases S-sulfhydration contributes to human skeletal muscle function.

Biochemical changes in progressive muscular dystrophy. XII. Cyclic nucleotides in lymphoid and nonlymphoid organs of dystrophic mice

Contact Info

Product

Resources

About