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1.
  • 1.1. In both 2- and 3-month-old 129 ReJ mice, the catalytic activity levels of three enzymes involved in glycogen breakdown (phosphorylase, enolase, and aldolase) were found to be 35–50% lower in hind limb muscles of dystrophic mice as compared with normal mice.
  • 2.2. The reduced activities of these enzymes in the diseased tissue was directly due to corresponcling reductions in the number of enzyme molecules rather than being due to inactivation of the enzymes in the dystrophic muscle.
  • 3.3. Results of short term double isotope incorporation experiments conducted with muscle expiants in vitro suggested that the rates of synthesis of these enzymes, and of most other abundant cytosolic proteins, relative to each other, were similar in hind limb muscles of normal and dystrophic mice.
  • 4.4. The present work on murine muscular dystrophy is discussed in terms of our previous studies into the influence of avian muscular dystrophy on the content and synthesis of abundant glycolytic enzymes in chicken skeletal muscles.
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2.
In order to investigate the behavior of hydrolytic enzymes in chronic infections, the activities of 17 hydrolytic enzymes were tested in limb muscles, heart muscle, spleen, liver, and kidney of lepromatous mice infected with Mycobacterium lepraemurium (M. lepraemurium) and their controls. Typical increases in those enzymatic activities were seen in spleen and liver, where pathological changes were the most pronounced, especially at the 11th week after the inoculation of the bacilli. At the 16th week, the enzymatic changes became less remarkable probably because of the decreased viability of tissues in these organs. The enzymatic changes observed could not be explained as due to bacterial enzymes. These findings are compatible with the notion that the increases in hydrolytic enzyme activities are related to tissue damage caused by murine leprosy.  相似文献   

3.
The present study was undertaken to elucidate further the enzymatic changes in dystrophic muscle using multivariate analysis. The activities of 14 kinds of enzymes, including 6 exopeptidases, 4 endopeptidases, beta-N-acetyl-D-glucosaminidase, phosphatase, esterase, and ribonuclease, were examined in forelimb and hindlimb muscles as well as in cardiac muscle of dystrophic mice and their controls. Two principal components identified from the enzymatic spectrum proved to be related especially to aminopeptidases and to serine proteinases, respectively. The enzymatic changes in forelimb muscle were very similar to those in hindlimb muscle when both were compared to those in cardiac muscle. The changes in aminopeptidases were unique to the limb muscles, whereas those of serine proteinases were unique to cardiac muscle of dystrophic mice. In the future, more attention should be focused on the role of exopeptidases in pathogenetic mechanisms of muscular dystrophy, because of the possibility that they play a major role in the initial stage of muscular dystrophy.  相似文献   

4.
In order to gain an insight into the pathogenesis of mouse muscular dystrophy, we investigated the natural suppressor serine tRNA. The natural suppressor seryl-tRNA was distinguished from the other seryl-tRNAs on the basis of its specific property of being converted into phosphoseryl-tRNA by a tRNA kinase. On a wet-weight basis, the content of total tRNA in dystrophic muscles was 47% of that in normal muscles. Although the serine-accepting activities of tRNA were similar in muscles of 3-month-old dystrophic and normal mice, the ratio of [32P]phosphoseryl-tRNA (suppressor tRNA) to the total serine tRNA was significantly enhanced in dystrophic muscles compared with that in normal muscles. This high content of suppressor tRNA in dystrophic muscles was further confirmed by dot-blot hybridization experiments with the DNA probes CGTAGTCGGCAGGAT and CGCCCGAAAGGTGGAA for major tRNA(IGASer) and suppressor tRNA respectively. At the early postnatal age of 3 weeks, when only a week had elapsed since the first manifestation of the dystrophic symptom (hindleg dragging), the ratio of suppressor tRNA to major tRNAs in dystrophic hindleg muscles was abnormally increased. Thereafter it decreased with age in normal mice but remained almost unchanged in dystrophic mice. Consequently, at 3 months old, it was 1.7 times higher in dystrophic than in normal mice. The suppressor tRNA is now accepted to play a role in the synthesis of glutathione peroxidase. The present study showed that the content of this enzyme was abnormally elevated in dystrophic mice. Previously we had demonstrated that the docosahexaenoic (C22:6) acid content in phospholipids was decreased, possibly resulting from the enhanced oxidative milieu caused by the dystrophic condition. Thus far, the findings suggest that an increase in the contents of suppressor tRNA and glutathione peroxidase in dystrophic muscle may have been secondarily induced by such a highly oxidative state in the dystrophic condition. However, it is difficult to exclude the possibility that the natural suppressor tRNA plays a primary role in the pathogenesis of muscular dystrophies.  相似文献   

5.
Summary The activity of acid phosphatase in skeletal muscle fibres of the plantaris and soleus of normal and dystrophic male hamsters was quantified using a histochemical post-coupling semipermeable membrane technique. Althoug the absolute levels of activity were found to vary widely from one animal to another, the ratio of the mean activities in the two muscles in each animal was virtually constant. In normal muscles, the ratio was about 0.73 and in dystrophic muscles, about 0.77. The activity in plantaris muscle fibres was always significantly lower than that in the corresponding soleus fibres, and in normal fibres compared to dystrophic ones. Another difference was that in normal fibres the mean activity declined to a constant level in mature animals older than about 3 months. In contrast, the activity in dystrophic muscles appeared to fall exponentially throughout life. The functional significance of these findings is discussed.In honour of Prof. P. van Duijn  相似文献   

6.
The activity of acid phosphatase in skeletal muscle fibres of the plantaris and soleus of normal and dystrophic male hamsters was quantified using a histochemical post-coupling semipermeable membrane technique. Although the absolute levels of activity were found to vary widely from one animal to another, the ratio of the mean activities in the two muscles in each animal was virtually constant. In normal muscles, the ratio was about 0.73 and in dystrophic muscles, about 0.77. The activity in plantaris muscle fibres was always significantly lower than that in the corresponding soleus fibres, and in normal fibres compared to dystrophic ones. Another difference was that in normal fibres the mean activity declined to a constant level in mature animals older than about 3 months. In contrast, the activity in dystrophic muscles appeared to fall exponentially throughout life. The functional significance of these findings is discussed.  相似文献   

7.
In a study of 58 patients with various diseases of muscle or of the neuromuscular system, the serum activity of various enzymes was measured. Abnormal elevation of serum activities of aldolase, lactic dehydrogenase and, to a lesser extent, glutamic-oxalacetic transaminase and phosphohexose isomerase, was an almost constant feature in patients with progressive muscular dystrophy. These elevations were very frequent in dermatomyositis, common in acute cerebral vascular accidents, and rarely seen in other neurological disorders. Abnormal serum activity of iso-citric dehydrogenase was not observed in the course of the present study.Supplementary protein feeding of patients with muscular dystrophy had no effect on serum enzyme activity, no consistent effect on urinary creatine excretion and no effect on the strength of the patient or the course of the disease.Dystrophic muscles from a dystrophic strain of mice showed a decrease in activity of lactic dehydrogenase and aldolase below that of control muscle and an increase of iso-citric dehydrogenase activity. These findings, taken with the differences in serum activities of lactic dehydrogenase, aldolase and isocitric dehydrogenase in the dystrophic animals, support the conclusion that dystrophic animals handle these soluble enzymes in quite different ways.  相似文献   

8.
In a study of 58 patients with various diseases of muscle or of the neuromuscular system, the serum activity of various enzymes was measured. Abnormal elevation of serum activities of aldolase, lactic dehydrogenase and, to a lesser extent, glutamic-oxalacetic transaminase and phosphohexose isomerase, was an almost constant feature in patients with progressive muscular dystrophy. These elevations were very frequent in dermatomyositis, common in acute cerebral vascular accidents, and rarely seen in other neurological disorders. Abnormal serum activity of iso-citric dehydrogenase was not observed in the course of the present study. Supplementary protein feeding of patients with muscular dystrophy had no effect on serum enzyme activity, no consistent effect on urinary creatine excretion and no effect on the strength of the patient or the course of the disease. Dystrophic muscles from a dystrophic strain of mice showed a decrease in activity of lactic dehydrogenase and aldolase below that of control muscle and an increase of iso-citric dehydrogenase activity. These findings, taken with the differences in serum activities of lactic dehydrogenase, aldolase and isocitric dehydrogenase in the dystrophic animals, support the conclusion that dystrophic animals handle these soluble enzymes in quite different ways.  相似文献   

9.
Section of sciatic nerves of rats produced fibrillations within 3 days. Foci of hyalination leading to necrosis corresponded to segments of muscles containing end plates. The electrolyte content, mainly Ca, was increased, NADH2-TR activity was decreased and membrane ATP-ase was increased. The known increase in hydrolytic enzyme activities in denervated muscles was due to spilling of lysosomal enzymes from degenerating axons at the myoneural junction. This explains the discrepancy between morphological studies indicating paucity of lysosomes in normal muscles and the high hydrolytic enzyme activities in denervation. We propose that denervation changes are at least partly due to the effect of lysosomal spillage from degenerating axons.  相似文献   

10.
Summary Section of sciatic nerves of rats produced fibrillations within 3 days. Foci of hyalination leading to necrosis corresponded to segments of muscles containing end plates. The electrolyte content, mainly Ca, was increased, NADH2-TR activity was decreased and membrane ATP-ase was increased.The known increase in hydrolytic enzyme activities in denervated muscles was due to spilling of lysosomal enzymes from degenerating axons at the myoneural junction. This explains the discrepancy between morphological studies indicating paucity of lysosomes in normal muscles and the high hydrolytic enzyme activities in denervation. We propose that denervation changes are at least partly due to the effect of lysosomal spillage from degenerating axons.  相似文献   

11.
1. Skeletal muscle from C57BL dystrophic mice demonstrated decreased activities of acetylcholinesterase with increased activities of butyrylcholinesterase. These changes were less distinct when compared to those observed with 129 ReJ mice. 2. Collagenase or trypsin treatment solubilized less acetylcholinesterase activity but more butyrylcholinesterase activity from muscle of C57BL dystrophic mice than from muscle of control mice. 3. These treatments resulted in similar pattern of release of acetylcholinesterase activity from muscle of 129 ReJ mice, except that more acetylcholinesterase activity was released from dystrophic muscle (129 ReJ) than from control by pepsin treatment. 4. The acetylcholinesterase activities released by proteolytic enzymes were characterized by sucrose density gradient centrifugation.  相似文献   

12.
White and red muscles of normal and genetically dystrophic chickens were compared with regards to activity levels of three soluble enzymes, glyceraldehyde-3-phosphate dehydrogenase, creatine phosphokinase, and acetyl phosphatase. In dystrophic white muscle (pectoral), activity of the two sulfhydryl enzymes, glyceraldehyde-3-phosphate dehydrogenase and creatine phosphokinase, was preferentially lost from the sarcoplasm resulting in decreased specific activities. By contrast, acetyl phosphatase was preferentially retained and showed increased specific activity. Dystrophic white muscle had decreased sulfhydryl content in the soluble proteins, severe reduction in muscle mass, fatty infiltration, and fragmentation of fibers. Red dystrophic muscles (thigh) were minimally involved in accordance with the known sparing of red fibers. Enzyme activities were correlated with histological observations. The results suggested that the disease process in dystrophic white muscle may be related to alterations in the sulfhydryl groups of proteins. The data are correlated with the beneficial effects of our treatment of hereditary avian dystrophy with the sulfhydryl compound, penicillamine (Chou, T.H., Hill, E.J., Bartle, E., Woolley, K., LeQuire, V., Olson, W., Roelofs, R., and Park, J.H. (1975) J. Clin. Invest. 56, 842-849).  相似文献   

13.
In order to understand the pathogenesis of mouse muscular dystrophy, we investigated the levels of the thiobarbituric acid-reactive substances (TBARS), H2O2 and NADPH oxidase activity, which were relative to the acceleration of oxidative conditions, in tongue and hindleg skeletal muscles from C57BL/6J-dy mice. The TBARS content (702 nmol/g protein) in skeletal muscles from 2-months-old dystrophic mice was increased significantly over that (384 nmol/g protein) in muscles from age-matched normal mice. The H2O2 concentration in dystrophic skeletal muscles was 30% higher than that in normal ones. Microsomal NADPH oxidase activity which was related to the production of superoxide anions, was similar between dystrophic muscles (4.66 nmol/10 min/mg protein) and normal muscles (4.11 nmol/ 10 min/mg protein). These results indicate that oxidation is accelerated in the dystrophic muscles. However, the TBARS content in the tongues of dystrophic mice was identical to that of normal mice. This finding supports our bone-muscle growth imbalance hypothesis for the pathogenesis of mouse muscular dystrophy.  相似文献   

14.
The precise mechanisms underlying skeletal muscle damage in Duchenne muscular dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation, with subsequent reperfusion during rest, has been documented. Therefore, one possibility is the presence of increased oxidative stress. We applied a model of acute hindlimb ischemia/reperfusion (I/R) in mdx mice (genetic homolog of DMD) to evaluate dynamic in vivo responses of dystrophic muscles to this form of oxidative stress. Before the application of I/R, mdx muscles showed: 1) decreased levels of total glutathione (GSH) with an increased oxidized (GSSG)-to-reduced (GSH) glutathione ratio; 2) greater activity of the GSH-metabolizing enzymes glutathione peroxidase (GPx) and glutathione reductase; and 3) lower activity levels of NADP-linked isocitrate dehydrogenase (ICDH) and aconitase, two metabolic enzymes that are sensitive to inactivation by oxidative stress and also implicated in GSH regeneration. Interestingly, nondystrophic muscles subjected to I/R exhibited similar changes in total glutathione, GSSG/GSH, GPx, ICDH, and aconitase. In contrast, all of the above remained stable in mdx muscles subjected to I/R. Taken together, these results suggest that mdx muscles are chronically subjected to increased oxidative stress, leading to adaptive changes that attempt to protect (although only in part) the dystrophic muscles from acute I/R-induced oxidative stress. In addition, mdx muscles show significant impairment of the redox-sensitive metabolic enzymes ICDH and aconitase, which may further contribute to contractile dysfunction in dystrophic muscles.  相似文献   

15.
Acetylcholinesterase (AChE; EC 3.1.1.7) activity and the distribution of its molecular forms were studied in the nervous system of normal and dystrophic 129/ReJ mice, including the sciatic-tibial nerve trunk and motor nerves to slow- and fast-twitch muscles. In normal mice, motor nerves to the slow-twitch soleus exhibited a low AChE activity together with a low level of G4 (10S form) as compared with nerves of the predominantly fast-twitch plantaris and extensor digitorum longus. In contrast, in dystrophic mice, the AChE activity as well as the G4 content of nerves to the fast-twitch muscles were low, displaying an AChE content similar to that of the nerve of the soleus muscle. In the sciatic-tibial nerve trunk, the AChE activity decreased along the nerve in an exponential mode, at rates that were similar in both conditions. However, in dystrophic mice, the AChE activity was reduced throughout the nerve length by a constant value of approximately 180 nmol/h/mg protein. Further analyses indicated that AChE in this nerve trunk was distributed among two compartments, a decaying and a constant one. The decay involved exclusively the globular forms. The activity of A12 (16S form) remained constant along the nerve and was similar in both normal and dystrophic mice. In addition, according to the equation describing the decay of AChE, the reduction in enzymatic activity observed in the dystrophic mice affected mainly G4 in the constant compartment. Brain, spinal cord, sympathetic ganglia, and serum, which were also examined, showed no remarkable differences between the two conditions in their G4 content. The AChE abnormalities that we found in nervous tissues of 129/ReJ dystrophic mice were confined to the motor system.  相似文献   

16.
Ca2+-uptake activities of the sarcoplasmic reticulum (SR) were determined with a Ca2+-sensitive electrode in homogenates from fast- and slow-twitch muscles from both normal and dystrophic mice (C57BL/6J strain) of different ages. Immunochemical quantification of tissue Ca2+-ATPase content allowed determination of the specific Ca2+-transport activity of the enzyme. In 3-week-old mice of the dystrophic strain specific Ca2+ transport was already significantly lower than in the normal strain. It progressively decreased with maturation and reached only 40-50% and 30-50% of the normal values in fast- and slow-twitch muscles of adult dystrophic animals, respectively. Tissue contents of calsequestrin were reduced in both types of muscle leading to an increased Ca2+-ATPase to calsequestrin protein ratio. Equal amounts of the Ca2+-ATPase protein (detected by Coomassie blue staining of polyacrylamide gels) were present in SR vesicles isolated by Ca2+-oxalate loading from adult normal and dystrophic fast-twitch muscles. However, the specific ATP-hydrolysing activity of the enzyme was approximately 50% lower in dystrophic than in normal SR. The reduced ATP-hydrolysing activity was correlated with decreased Ca2+-transport activity, phosphoprotein formation and fluorescein isothiocyanate labeling as determined in total microsomal and heavy SR fractions. Although the Ca2+ and ATP affinities of the enzyme were unaltered, its ATPase activity was reduced at all levels of ATP in the dystrophic SR. Taken together, these findings point to a markedly impaired function of the SR and an increase in the population of inactive SR Ca2+-ATPase molecules in murine muscular dystrophy.  相似文献   

17.
1. Experiments were carried out to examine the biochemical changes, such as contractile protein biochemistry and membrane bound enzyme alterations associated with skeletal muscles of myd/myd. 2. Our studies demonstrate that there was a progressive decline in myofibrillar ATPase activity, and this decrease is greatest in 30 weeks old animals of myd/myd as compared to controls. 3. The proteolytic activity of myofibrils isolated from myd/myd was significantly higher than controls. 4. There was no significant difference in Ca2+ ATPase activity of myosin and actin-activated myosin ATPase activity of myd/myd and their controls. 5. Mg2+ ATPase and Na(+)+K(+)-ATPase of myodystrophic SL showed significant increase compared to controls. 6. Isoproterenol stimulated adenylate cyclase activity was significantly lower in the SL of dystrophic mice compared to controls. 7. GTP+isoproterenol stimulate adenylate cyclase was significantly higher in control SL and SR when compared to SL and SR isolated from myd/myd. 8. Guanylate cyclase activity was greater in myodystrophic mice both in the absence and presence of Triton X-100. cGMP and cAMP phosphodiesterase activities were greater in dystrophic mice as compared to controls. 9. These observations suggest that there are significant changes in myofibrillar ATPase, myofibrillar protease and membrane bound enzymes of myd/myd compared to control.  相似文献   

18.
The level of nerve growth factor-like immunoreactivity in the lower limb muscles, the site where the dystrophic mice are effected, of both normal and dystrophic mice was studied by solid-phase radioimmunoassay. Nerve growth factor-like immunoreactivity levels of the homozygous dystrophic mice were about two times lower than those of the heterozygous dystrophic mice at 10–11 weeks and 7–8 weeks of age. The levels in 4–5 week old homozygous mice were too low for detection and remarkable differences between the homozygous and the heterozygous mice were observed at this age. These differences in the level of nerve growth factor-like immunoreactivity suggest that the factor may have some relation to the disease.  相似文献   

19.
The excretion of 3-methylhistidine increased in the urine of dystrophic mice C57BL/6J. The content of 3-methylhistidine residue decreased in the muscle proteins of dystrophic mice, but not in other organs. Methylated proteins in the skeletal muscle, actin and myosin, were partially purified from the dystrophic and control muscles. The amount of 3-methylhistidine residue in unit weight of the actin and myosin preparations was normal in dystrophic muscle. These three facts indicate that the turnover rates of actin and myosin are increased in the muscle of the dystrophic mice.  相似文献   

20.
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.  相似文献   

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