Defect in regulation of membrane transport of monosaccharides in dystrophic muscle

1979 ◽  
Vol 57 (7) ◽  
pp. 695-701 ◽  
Author(s):  
J. Elbrink
Keyword(s):  
Plasma Membranes ◽  
Sugar Transport ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Variable Effect ◽  
Cardiomyopathic Hamsters ◽  
Uncoupling Of Oxidative Phosphorylation ◽  
Dystrophic Mice ◽  
Normal Controls ◽  
Glucose Analogue

The penetration of a nonmetabolized glucose analogue, 3-O-methyl-D-glucose, across the plasma membranes of tissues from dystrophic mice and cardiomyopathic (dystrophic) hamsters has been compared with that of normal controls. Under basal conditions the penetration of test sugar was similar in lens and diaphragm of normal and dystrophic 129/ReJ mice. Stimulation of sugar transport by 2,4-dinitrophenol did occur in normal but not in dystrophic diaphragm. A submaximal concentration of insulin had a more variable effect in dystrophic than in normal muscle while a supramaximal concentration of the hormone increased the uptake of the glucose analogue to an equal extent in the two tissues. In the BIO 14.6 strain of cardiomyopathic hamsters, uncoupling of oxidative phosphorylation did not increase sugar transport in extensor digitorum longus muscles, while the normal effect was observed in dystrophic soleus and in both these muscles of the random bred controls. The absence of an effect by a condition simulating anoxia suggests that in dystrophy, certain muscles are unable to accelerate the entry of glucose when this is required.

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.

PROTEOLYTIC ENZYMES IN NORMAL AND DYSTROPHIC MOUSE MUSCLE

1966 ◽  
Vol 44 (5) ◽  
pp. 613-623 ◽  
Author(s):  
L. Berlinguet ◽  
U. Srivastava
Keyword(s):  
Proteolytic Enzymes ◽  
Chemical Change ◽  
Optimum Conditions ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Muscle Enzymes ◽  
Mouse Muscle ◽  
Ph Values ◽  
Dystrophic Mouse ◽  
Dystrophic Mice

Proteolytic enzymes extracted from normal and dystrophic mouse muscle were studied, and optimum conditions for their activities were established. It was found that these enzymes were active at two pH values, 7.5 and 9. In normal and dystrophic mice, the enzymatic activity increased with age. When the activities of dystrophic muscle enzymes were compared with those of normal muscle enzymes, the increase was most significant in animals 60–90 days of age. The results obtained when the enzymes extracted from normal or dystrophic muscle were incubated with substrates from normal or dystrophic muscle indicate that the defect in the muscle is due to an increase in the activities of the proteolytic enzymes rather than to a chemical change in the muscle proteins.

Ca2+-dependent slow action potentials in normal and dystrophic mouse skeletal muscle

1983 ◽  
Vol 245 (5) ◽  
pp. C415-C422 ◽  
Author(s):  
L. M. Kerr ◽  
N. Sperelakis
Keyword(s):  
Skeletal Muscle ◽  
Action Potentials ◽  
Osmotic Shock ◽  
Muscle Fibers ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Recording Technique ◽  
Mammalian Muscle ◽  
Dystrophic Mice ◽  
Slow Action Potentials

Slowly rising action potentials (APs), previously described in amphibian skeletal muscle, were examined in skeletal muscle of normal and dystrophic mice (129/ReJ strain). A standard two-microelectrode recording technique was used. Muscles were bathed in a solution that was Cl- free (methanesulfonate substituted), high in K+ (20 mM), and contained 15 mM tetraethylammonium. The slow APs were elicited under conditions in which the fast Na+ channels were voltage inactivated (by partial depolarization) and in which the external Na+ concentration was only 10 mM. Increases in external Ca2+ concentration produced increases in slow AP amplitude and duration. Mn2+ (4 mM), La3+ (4 mM), and detubulation with osmotic shock blocked the slow APs. When slow APs were generated at 30-s intervals, their amplitude stayed constant. When they were generated at 15-s intervals, their amplitude decreased progressively and then fell to zero by the 11th stimulus. The Ca antagonists verapamil (10(-5) M) and bepridil (10(-5) M) caused this decrease in amplitude to occur more quickly. Voltage inactivation of the slow APs occurred between -45 and -10 mV. Slow APs recorded from dystrophic muscle fibers were decreased in amplitude and duration compared with those in normal fibers, and there was a reduced incidence of occurrence; 96% of the fibers in normal muscle exhibited slow APs compared with only 46% of dystrophic muscle fibers. In summary, slow Ca2+ APs in mammalian muscle are similar to those in cardiac and amphibian skeletal muscle, and these slow APs are depressed in dystrophic skeletal muscle.

Thiol protease and cathepsin D activities in selected tissues and cultured cells from normal and dystrophic mice

1987 ◽  
Vol 65 (2) ◽  
pp. 124-129 ◽  
Author(s):  
P. Gopalan ◽  
M. J. Dufresne ◽  
A. H. Warner
Keyword(s):  
Protease Inhibitors ◽  
Protease Activity ◽  
Cathepsin D ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Thiol Protease ◽  
Hindlimb Muscle ◽  
Protease Activation ◽  
Dystrophic Mice ◽  
Cathepsin D Activity

Thiol protease and cathepsin D activities were studied in extracts from hindlimb muscle of 60-day-old normal and dystrophic mice, strain 129 ReJ, and from cultured normal and dystrophic cells. Total thiol protease activity in dystrophic muscle extracts was 3.5 times higher than in normal muscle extracts, while cathepsin D, activity was 2.2 times greater in dystrophic muscle compared with normal muscle. Activation (pH 4.5, 30 °C) of latent thiol protease activity in extracts of muscle occurred concomitant with the inactivation or dissociation of endogenous protease inhibitors. Thiol protease assays revealed a higher ratio of active to inactive protease activity in extracts from dystrophic muscle than from normal muscle. Cultured myoblasts (L69/1) were found to contain 30-fold more thiol protease(s) and 6-fold more cathepsin D activity than whole muscle. Cells established from dystrophic muscle and grown in culture for periods up to 6 months were more responsive to thiol protease activation conditions than similar cultures derived from normal muscle. From data on the rate and extent of thiol protease activation in extracts from dystrophic cells and hindlimb muscle compared with normal tissue, it appears that cells and tissues from dystrophic mice contain a lower level of protease inhibitors than cells and tissues from normal mice.

EFFECT OF VARIOUS AMINO ACIDS ON THE INCORPORATION OF 14C-L-LEUCINE IN THE TISSUE PROTEINS OF NORMAL AND DYSTROPHIC MICE

1967 ◽  
Vol 45 (12) ◽  
pp. 1985-1993 ◽  
Author(s):  
Louis Berlinguet ◽  
Uma Srivastava
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Actinomycin D ◽  
Daily Injection ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Time Intervals ◽  
Parallel Group ◽  
Continuous Injection ◽  
Dystrophic Mice

Normal and dystrophic mice received daily injections of either water, saline, glutamate, aspartate, glycine, ACPC, or actinomycin D for 5 days. One parallel group of animals received no injections and served as control. On the 6th day after the start of the experiment, all the animals received an intravenous injection of 14C-L-leucine and were killed at various time intervals, ranging from 4 h to 12 days. Daily injections of water or saline to the animals did not cause any change in the incorporation of 14C-L-leucine into various tissue proteins. Glutamate administration increased the retention of 14C-L-leucine in normal muscle but not in dystrophic muscle. A daily injection of aspartate increased the retention of the radioactive amino acid in both normal and dystrophic muscles, the higher increase being found in the dystrophic muscle. Administration of glycine reduced the turnover of proteins in both normal and dystrophic muscles. ACPC (1-amino-cyclopentanecarboxylic acid) or actinomycin D administration caused a decrease in the incorporation of 14C-L-leucine into normal and dystrophic muscles.The continuous injection of glutamate or aspartate for 8 days after the 14C-L-leucine administration caused a very large increase in the retention of the labelled amino acid into the proteins of various tissues of normal and dystrophic mice. It is concluded that variations in the amino acid pools can modify the turnover of proteins, which can be of importance in muscular dystrophy.

Enzyme studies of skeletal muscle in mice with hereditary muscular dystrophy

1963 ◽  
Vol 205 (5) ◽  
pp. 897-901 ◽  
Author(s):  
Marilyn W. McCaman
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Glutathione Reductase ◽  
Enzyme Activities ◽  
Lactic Dehydrogenase ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Nerve Section ◽  
Mouse Muscle ◽  
Dystrophic Mouse

The activities of 20 enzymes in normal, heterozygous, and dystrophic mouse muscle were studied by means of quantitative microchemical methods. Enzyme activities in normal and heterozygous muscle were essentially the same. In dystrophic muscle glucose-6-P dehydrogenase, 6-P-gluconic dehydrogenase, glutathione reductase, peptidase, ß-glucuronidase, and glucokinase activities were significantly higher than in normal muscle, while α-glycero-P dehydrogenase and lactic dehydrogenase activities were significantly lower. The pattern of enzyme activities found in normal gastrocnemius denervated by nerve section was strikingly similar to that in dystrophic muscle.

Stretch-induced growth in chicken wing muscles: effects on hereditary muscular dystrophy

1982 ◽  
Vol 242 (3) ◽  
pp. C178-C183 ◽  
Author(s):  
C. R. Ashmore
Keyword(s):  
Muscular Dystrophy ◽  
Normal Values ◽  
Muscle Growth ◽  
Cross Sectional Area ◽  
Muscle Pathology ◽  
Sectional Area ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Cross Sectional ◽  
Passive Stretch

Skeletal muscle growth induced by passive stretch was characterized in the Patigialis muscle of chicks with hereditary muscular dystrophy. When the muscle of 6-wk-old chicks was stretched for 1 wk, the effects on muscle growth and on muscle pathology were variable, but in general few differences between stretched and unstretched muscles were observed. However, when the muscle of 1-wk-old chicks was stretched for 6 wk, the effects on muscle growth and on prevention of pathology were dramatic. Similar to results obtained previously when normal chick muscles were stretched [Holly et al., Am. J. Physiol. 238 (Cell Physiol. 7): C62-C71, 1980; Barnett et al., Am. J. Physiol. 239 (Cell Physiol. 8): C39-C46, 1980], stretched dystrophic muscle increased in weight (200%), cross-sectional area (107%), and fiber cross-sectional area (82%). DNA concentration, which is severalfold higher in unstretched dystrophic muscle compared with unstretched normal muscle, fell to values not different from normal values after being stretched. Nuclei per square millimeter also were the same for stretched dystrophic and stretched normal muscle. Histograms indicated that stretching induced a fiber distribution in dystrophic muscle qualitatively similar to that found in stretched normal muscle. Cytochemical observations revealed a dramatic protective effect of stretch against the progressive pathology of dystrophy. It is concluded that stretch of muscle applied to newly hatched dystrophic chicks is a powerful deterrent of symptoms characteristic of hereditary muscular dystrophy. Stretch imposed after the symptoms of dystrophy are apparent provides little, if any, protection.

Effects of denervation on normal and dystrophic muscle: DNA and nucleotide enzymes

1965 ◽  
Vol 209 (3) ◽  
pp. 495-500 ◽  
Author(s):  
M. W. McCaman ◽  
R. E. McCaman
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Nucleotide Metabolism ◽  
Purine Nucleoside ◽  
Denervated Muscle ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
P Values ◽  
Nucleoside Phosphorylase ◽  
Dystrophic Mouse ◽  
Protein Versus

The activities of five enzymes associated with nucleotide metabolism, as well as values for protein and DNA-P, in homogenates from normal, dystrophic, and denervated (3–46 days) normal and dystrophic mouse gastrocnemii have been reported. When the data were expressed per muscle, the following observations were made: protein was much lower in dystrophic than in normal muscle and decreased in both muscles after denervation; DNA-P values remained relatively constant in normal muscle after denervation whereas the values in dystrophic muscle were slightly lower; adenylic deaminase activity decreased rapidly and profoundly after denervation of normal muscle, approaching values found in dystrophic muscle; purine nucleoside phosphorylase and 5-nucleotidase activities were similar in normal and dystrophic muscle and remained relatively constant after denervation; Ca- and Mg-ATPase activities were considerably lower in dystrophic muscle and decreased in both normal and dystrophic muscle after denervation. The different interpretations of the same data which are possible by expressing data per unit protein versus per muscle were discussed. These results confirm earlier studies which demonstrated the striking biochemical similarity between dystrophic and denervated muscle.

Neuromuscular transmission in dystrophic mice

1977 ◽  
Vol 40 (4) ◽  
pp. 836-843 ◽  
Author(s):  
S. Carbonetto
Keyword(s):  
Neuromuscular Transmission ◽  
Neuromuscular Junctions ◽  
Large Population ◽  
Muscle Fibers ◽  
Dystrophic Muscle ◽  
Quantum Content ◽  
Quantal Size ◽  
Significant Difference ◽  
Release Of Acetylcholine ◽  
Dystrophic Mice

1. Neuromuscular transmission was studied in the extensor digitorum-longus muscle of dystrophic mice (strain 129/ReJ) by means of intracellular recording techniques. 2. In a large population of normal and dystrophic muscle fibers tested, the incidence of transmission failure was about 2% and showed no significant difference between the two groups. 3. Quantal size and quantum content of dystrophic junctions were found to be normal. This was true even of nerve terminal on apparently atrophied muscle fibers. 4. The facilitation ratio at dystrophic junctions was not significantly different from normal. 5. Dystrophic neuromuscular junctions exhibited an abnormality high frequency of giant spontaneous potentials. Application of tetrodotoxin (10(-6) M) and curare (10(-6) M) indicated that these potentials were caused by impulse-independent release of acetylcholine. 6. Neuromuscular transmission in dystrophic mice was found functionally normal and unrelated to the degenerative state of the muscle.

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