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

1986 ◽  
Vol 64 (12) ◽  
pp. 1339-1348 ◽  
Author(s):  
Manohar Thakur ◽  
Mikael Sebag ◽  
Uma Srivastava
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Cyclic Nucleotides ◽  
Significant Variation ◽  
Lymphoid Organs ◽  
Immune Responsiveness ◽  
Sharp Decline ◽  
Progressive Muscular Dystrophy ◽  
Camp And Cgmp ◽  
Dystrophic Mice

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.

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

1981 ◽  
Vol 59 (4) ◽  
pp. 329-334 ◽  
Author(s):  
Uma Srivastava ◽  
Mikael Sebag ◽  
Manohar Thakur
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Cardiac Muscle ◽  
Cyclic Nucleotides ◽  
Dystrophic Muscle ◽  
Camp Content ◽  
Progressive Muscular Dystrophy ◽  
Camp And Cgmp ◽  
Dystrophic Mice ◽  
Murine Dystrophy

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.

Biochemical Changes in Progressive Muscular Dystrophy. IX. Synthesis of Native Myosin, Actin, and Tropomyosin in the Skeletal Muscle of Mouse as a Function of Muscular Dystrophy

1972 ◽  
Vol 50 (4) ◽  
pp. 409-415 ◽  
Author(s):  
Uma Srivastava
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Protein Purification ◽  
Gel Electrophoresis ◽  
Dystrophic Muscle ◽  
Mouse Muscle ◽  
Progressive Muscular Dystrophy ◽  
Dystrophic Mice

The synthesis of native myosin, actin, and tropomyosin in the skeletal muscle of normal and hereditary dystrophic mice was studied with the help of direct counting as well as acrylamide-gel electrophoresis and protein purification procedures.Labelling of the nascent protein indicated that heavier polysomes from the normal muscle were able to incorporate more radioactivity into the protein than the heavier polysomes from the dystrophic muscles. Contrary to this, lighter polysomes in the dystrophic muscle demonstrated higher incorporation as compared to the normal.Results of in vivo and in vitro incorporation as well as those of acrylamide-gel electrophoresis and protein purification procedures indicated that synthesis of myosin decreased in the dystrophic muscle. The synthesis of actin did not show a significant change either in normal or dystrophic muscle, whereas that of tropomyosin increased sharply in the dystrophic mouse muscle.

BIOCHEMICAL CHANGES IN PROGRESSIVE MUSCULAR DYSTROPHY: VI. INCORPORATION OF URIDINE-2-14C INTO RNA OF VARIOUS TISSUE OF NORMAL AND DYSTROPHIC MICE

1967 ◽  
Vol 45 (9) ◽  
pp. 1419-1425 ◽  
Author(s):  
Uma Srivastava
Keyword(s):  
Muscular Dystrophy ◽  
Soluble Fraction ◽  
Normal Liver ◽  
Biochemical Changes ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Progressive Muscular Dystrophy ◽  
Dystrophic Mice

Normal and dystrophic mice were injected intravenously with uridine-2-14C at various stages of the disease. Radioactivity in the acid-soluble fraction of most of the tissues studied was unchanged or not significantly different in dystrophic animals. In vivo incorporation of uridine-2-14C into RNA increased in dystrophic muscle as compared to normal muscle at 30 days, remained the same at 60 days, and was reduced at 90 days. Similar results were also observed on the in vitro incorporation of uridine-2-14C catalyzed by homogenates of normal and dystrophic muscle. Dystrophic brain and pancreas showed a decrease in the incorporation at each stage investigated as compared to controls. No change in the incorporation was noted in dystrophic and normal liver, kidney, spleen, and heart. The decrease in uridine-2-14C incorporation in dystrophic muscle at 90 days could be due to an increased RNA content. Such a phenomenon was explained as due to infiltration of dystrophic muscle by invading macrophages.It is concluded that the metabolism of RNA is not decreased in the dystrophic muscle in preliminary stages of the disease as compared to the control.

Concentrations of K and Na in Skeletal Muscle of Mice With a Hereditary Myopathy (Dystrophia Muscularis)

1958 ◽  
Vol 193 (3) ◽  
pp. 530-533 ◽  
Author(s):  
Nome Baker ◽  
William H. Blahd ◽  
P. Hart
Keyword(s):  
Skeletal Muscle ◽  
Vitamin E ◽  
Muscular Dystrophy ◽  
Extracellular Space ◽  
Partial Replacement ◽  
Vitamin E Deficiency ◽  
Normal Value ◽  
Hereditary Myopathy ◽  
The Mean ◽  
Dystrophic Mice

Exchangeable body potassium (Ke), muscle potassium and muscle sodium concentrations have been measured in hereditarily dystrophic mice and in their normal littermates. Both Ke and K39/gm muscle were depressed in the dystrophics approximately 20% below the mean normal value; however, the concentration of Na23/gm muscle was higher by 50%, on the average, in the dystrophic tissue. The data suggest a partial replacement of intracellular by extracellular space in the dystrophic mice. Thus, this form of hereditary muscular dystrophy is qualitatively similar, with regard to K and Na concentrations, to human muscular dystrophy, vitamin E deficiency in rabbits, nutritional dystrophy in calves, and denervation in puppies.

Biochemical changes in progressive muscular dystrophy. XIII. Nucleic acids, proteins, and total nucleotides in the thymus and spleen of dystrophic mice

1985 ◽  
Vol 63 (5) ◽  
pp. 325-332 ◽  
Author(s):  
Uma Srivastava ◽  
Mikael Sebag ◽  
Manohar Thakur
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Muscular Dystrophy ◽  
Free Amino Acid ◽  
Free Amino ◽  
Specific Activity ◽  
Cellular Growth ◽  
Free Amino Acid Pool ◽  
Acid Pool ◽  
Dystrophic Mice

Assessments were made of the thymus and spleen weights and the total nucleotide, nucleic acid, and protein content as well as the incorporation of [14C]leucine into protein and of [3H]orotate into RNA, in the thymus, spleen, liver, brain, kidney, lungs, heart, pancreas, and skeletal muscle of normal (+/+) and dystrophic (dy/dy) 129 ReJ mice aged 40, 60, or 90 days. The weights of the thymus and spleen were lower at all stages of dystrophy. Total nucleotide and RNA levels per thymus were reduced at 90 days, while total DNA content was decreased at 60 and 90 days. Protein concentrations per thymus were diminished at each stage of the disease. The specific activity of the free amino acid pool and total free nucleotide pool did not show any significant variations in the thymus at any phase of dystrophy. Incorporation of [14C]leucine into protein and of [3H]orotate into RNA was considerably lower in the thymus at each stage of the disease. Total nucleotide content per spleen was decreased at 40 days, with no change at 60 days and followed by an increase at 90 days in the dystrophic mice. DNA, RNA, and protein levels were all reduced in the spleen at each stage of the disease. The specific activity of the free amino acid pool and total free nucleotide pool, as well as the incorporation of [14C]leucine into protein and of [3H]orotate into RNA, showed similar changes in the spleen as noted in the thymus at each phase of dystrophy. These observations indicate that significant alterations in cellular growth occur not only in skeletal muscle and other nonlymphoid organs, but also in the lymphoid organs of dystrophic mice. Such changes in the cellular growth of lymphoid organs could be responsible for an impairment of immunologic responses reflecting thymic atrophy in murine muscular dystrophy.

Effect of Δ9 tetrahydrocannabinol on cyclic nucleotides in synchronously dividing Tetrahymena

1981 ◽  
Vol 59 (7) ◽  
pp. 489-493 ◽  
Author(s):  
Selma Zimmerman ◽  
Arthur M. Zimmerman ◽  
Helen Laurence
Keyword(s):  
Cell Cycle ◽  
Nous Avons ◽  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Significant Variation ◽  
Experimental Treatment ◽  
Twofold Increase ◽  
Synchronized Cells ◽  
Free Running ◽  
Camp And Cgmp

Cyclic nucleotide levels were determined in division-synchronized Tetrahymena and the effect of Δ9-tetrahydrocannabinol (THC) on the cyclic nucleotide levels was studied. In non-drug-treated division-synchronized cells, there was no statistically significant variation in the level of cAMP and cGMP during the G2 period, preceding the first division. During the free running cell cycle (the interval of time between the first and second synchronous division) the twofold increase in the level of cAMP was statistically significant; however the variation in the level of cGMP was not statistically significant.THC caused a lowering of cAMP and cGMP levels throughout the 4-h experimental treatment. The suppression of cAMP and cGMP levels altered the cyclic nucleotide pattern of the cell cycle. The cAMP pattern was changed particularly in the G2 period preceding the first synchronous division, and immediately after division during the free running cell cycle. THC treatment caused division delays of approximately 8–15 min in the onset of the first and second synchronous division. However, the duration of the free running cell cycle (110–120 min) was unchanged. The suppression of cyclic nucleotide levels resulting from THC treatment is discussed in relation to delays in the division schedule.Nous avons déterminé le taux des nucléotides cycliques chez Tetrahymena se divisant de façon synchrone et nous avons étudié l'effet du Δ9-tétrahydrocannabinol (THC) sur le taux de ces nucléotides cycliques. Dans les cellules non traitées, se divisant de façon synchrone, il n'existe aucune variation statistiquement significative dans les teneurs du cAMP et du cGMP durant la période G2 précédant la première division. Durant le cycle cellulaire sans division (l'intervalle de temps entre la première et la seconde division synchrone), la teneur du cAMP augmente de deux fois, une augmentation statistiquement significative; cependant, la variation du taux du cGMP n'est pas statistiquement significative.

scholarly journals Reversal of cardiac and skeletal manifestations of Duchenne muscular dystrophy by cardiosphere-derived cells and their exosomes in mdx dystrophic mice and in human Duchenne cardiomyocytes

2017 ◽  
Author(s):  
Mark A. Aminzadeh ◽  
Russell G. Rogers ◽  
Kenneth Gouin ◽  
Mario Fournier ◽  
Rachel E. Tobin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Cardiac Function ◽  
Premature Death ◽  
Next Generation ◽  
Skeletal Myopathy ◽  
Genetic Deficiency ◽  
Dystrophic Mice

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy, affecting the heart as well as skeletal muscle. Here we report that cardiosphere-derived cells (CDCs), which are being tested clinically for the treatment of Duchenne cardiomyopathy, improve cardiac and skeletal myopathy in the mdx mouse model of DMD and in human Duchenne cardiomyocytes. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human Duchenne cardiomyocytes. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.

Cyclic Nucleotides in Progressive Muscular Dystrophy

1979 ◽  
Vol 18 (5) ◽  
pp. 356-360 ◽  
Author(s):  
Shozo Kito ◽  
Miyuki Yamamoto ◽  
Eiko Itoga ◽  
Takenobu Kishida
Keyword(s):  
Muscular Dystrophy ◽  
Cyclic Nucleotides ◽  
Progressive Muscular Dystrophy
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