scholarly journals Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

2015 ◽  
Vol 8 (5) ◽  
pp. 467-472 ◽  
Author(s):  
N. de Luna ◽  
A. Brull ◽  
J. M. Guiu ◽  
A. Lucia ◽  
M. A. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sodium Valproate ◽  
Glycogen Phosphorylase ◽  
Compensation Mechanism ◽  
Culture In Vitro ◽  
Mcardle Disease ◽  
Muscle Culture ◽  
The Brain

Neural regulation of cholinesterase in newt skeletal muscle. II. The effects of denervation and of culture in vitro

1979 ◽  
Vol 210 (3) ◽  
pp. 451-462 ◽  
Author(s):  
Michel P. Rathbone ◽  
John D. Vickers ◽  
Mailvaganam Ganagarajah ◽  
Judy A. Brown ◽  
David M. Logan
Keyword(s):  
Skeletal Muscle ◽  
Neural Regulation ◽  
Culture In Vitro

scholarly journals Systemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease

2019 ◽  
Vol 29 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Elyshia L McNamara ◽  
Rhonda L Taylor ◽  
Joshua S Clayton ◽  
Hayley Goullee ◽  
Kimberley L Dilworth ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Animal Model ◽  
Murine Model ◽  
Muscle Glycogen ◽  
Glycogen Phosphorylase ◽  
Large Animal ◽  
Mcardle Disease ◽  
Increased Risk ◽  
Virus Serotype ◽  
Functional Copy

Abstract McArdle disease is a disorder of carbohydrate metabolism that causes painful skeletal muscle cramps and skeletal muscle damage leading to transient myoglobinuria and increased risk of kidney failure. McArdle disease is caused by recessive mutations in the muscle glycogen phosphorylase (PYGM) gene leading to absence of PYGM enzyme in skeletal muscle and preventing access to energy from muscle glycogen stores. There is currently no cure for McArdle disease. Using a preclinical animal model, we aimed to identify a clinically translatable and relevant therapy for McArdle disease. We evaluated the safety and efficacy of recombinant adeno-associated virus serotype 8 (rAAV8) to treat a murine model of McArdle disease via delivery of a functional copy of the disease-causing gene, Pygm. Intraperitoneal injection of rAAV8-Pygm at post-natal day 1–3 resulted in Pygm expression at 8 weeks of age, accompanied by improved skeletal muscle architecture, reduced accumulation of glycogen and restoration of voluntary running wheel activity to wild-type levels. We did not observe any adverse reaction to the treatment at 8 weeks post-injection. Thus, we have investigated a highly promising gene therapy for McArdle disease with a clear path to the ovine large animal model endemic to Western Australia and subsequently to patients.

scholarly journals COMPARATIVE VIRULENCE OF ST. LOUIS ENCEPHALITIS VIRUS CULTURED WITH BRAIN TISSUE FROM INNATELY SUSCEPTIBLE AND INNATELY RESISTANT MICE

1941 ◽  
Vol 74 (5) ◽  
pp. 489-494 ◽  
Author(s):  
L. T. Webster ◽  
Mary S. Johnson
Keyword(s):  
Brain Tissue ◽  
High Titre ◽  
Encephalitis Virus ◽  
Similar Solution ◽  
Tyrode Solution ◽  
Culture In Vitro ◽  
The Brain

We find that St. Louis encephalitis virus cultured in 10 per cent serum-Tyrode solution plus brain tissue from 1-day-old innately susceptible mice attains a higher titre than when cultured in a similar solution plus brain tissue from 1-day-old closely related, yet innately resistant mice. This difference in titre persists regardless of whether the serum comes from innately susceptible or resistant mice. The relatively high titre of virus in the susceptible media is not affected by the addition of an extract (not cell-free) from the resistant brain; the relatively low titre of the virus in the resistant media may possibly be slightly enhanced by the addition of an extract from the susceptible brain. The findings as a whole show that the marked difference in the increase of St. Louis encephalitis virus in the brain tissue of innately susceptible and resistant mice, on culture in vitro, is due to some difference in the brain tissue itself.

Fish muscle glycogen phosphorylase

1968 ◽  
Vol 46 (5) ◽  
pp. 423-432 ◽  
Author(s):  
M. Yamamoto
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Phosphorylase ◽  
Active Form ◽  
Maximal Activity ◽  
Fish Muscle ◽  
Salmo Gairdneri ◽  
Rabbit Muscle ◽  
Muscle Phosphorylase

Glycogen phosphorylase b was purified 70- to 90-fold from skeletal muscle of rainbow trout (Salmo gairdneri). The purified enzyme exhibited maximal activity near pH 6.8 at 37°. Of several 5′-nucleotides tested, only 5′-AMP caused stimulation of phosphorylase b. The Km value for glucose-1-phosphate was 10–15 mM, and for 5′-AMP, 0.2–0.4 mM. Glucose (25 mM) and ATP (5 mM) were both inhibitory, but glucose-6-phosphate (5 mM) had no effect. Inactive trout muscle phosphorylase was converted to the active form in vivo by subjecting a fish to physical exercise. The conversion of fish muscle phosphorylase b to a was also catalyzed in vitro with purified rabbit muscle phosphorylase b kinase in the presence of ATP and Mg++. Evidence is presented to indicate the presence of phosphorylase b kinase and phosphorylase phosphatase in trout skeletal muscle.

Skeletal muscle glycogen phosphorylase akinetics: effects of adenine nucleotides and caffeine

2001 ◽  
Vol 91 (5) ◽  
pp. 2071-2078 ◽  
Author(s):  
James W. E. Rush ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Glycogen Phosphorylase ◽  
Adenine Nucleotides ◽  
Dependent Manner ◽  
Skeletal Muscle Glycogen ◽  
Sparing Effect ◽  
Dose Dependent ◽  
Glycogen Sparing

This study aimed to determine physiologically relevant kinetic and allosteric effects of Pi, AMP, ADP, and caffeine on isolated skeletal muscle glycogen phosphorylase a (Phos a). In the absence of effectors, Phos a had V max = 221 ± 2 U/mg and K m = 5.6 ± 0.3 mM Pi at 30°C. AMP and ADP each increased Phos a V max and decreased K m in a dose-dependent manner. AMP was more effective than ADP (e.g., 1 μM AMP vs. ADP: V max = 354 ± 2 vs. 209 ± 8 U/mg, and K m = 2.3 ± 0.1 vs. 4.1 ± 0.3 mM). Both nucleotides were relatively more effective at lower Pi levels. Experiments simulating a range of contraction (exercise) conditions in which Pi, AMP, and ADP were used at appropriate physiological concentrations demonstrated that each agent singly and in combination influences Phos a activity. Caffeine (50–100 μM) inhibited Phos a( K m ∼8–14 mM, ∼40–50% reduction in activity at 2–10 mM Pi). The present in vitro data support a possible contribution of substrate (Pi) and allosteric effects to Phos a regulation in many physiological states, independent of covalent modulation of the percentage of total Phos in the Phos a form and suggest that caffeine inhibition of Phos a activity may contribute to the glycogen-sparing effect of caffeine.

Effect of carbonic anhydrase III inhibition on substrate utilization and fatigue in rat soleus

1993 ◽  
Vol 71 (3-4) ◽  
pp. 277-283 ◽  
Author(s):  
Claude Côté ◽  
Hélène Riverin ◽  
Marie-Josée Barras ◽  
Roland R. Tremblay ◽  
Pierre Frémont ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Carbonic Anhydrase ◽  
Muscle Glycogen ◽  
Glycogen Phosphorylase ◽  
Physiological Solution ◽  
Bathing Solution ◽  
Type I ◽  
Fatigue Protocol ◽  
Carbonic Anhydrase Iii

Carbonic anhydrase III (CA III; EC 4.2.1.1) is the most abundant cytosolic enzyme in type I skeletal muscle fibers. We have previously shown that inhibiting the CA III activity of type I muscle can influence fatigability. Our goal was to test the hypothesis that the influence on fatigability of CA III inhibition is linked to an increased utilization of carbohydrates. Rat soleus muscles were incubated in vitro in a physiological solution with or without CA inhibitor (methazolamide, 1 mM) and submitted to a fatigue protocol. When the bathing solution contained glucose, the muscles incubated with methazolamide maintained a higher level of tension production than control muscles for the first 55–60 min of the test compared with 35–40 min when glucose was not added. Measurement of muscle glycogen content revealed that muscles incubated with CA inhibitor were utilizing their glycogen at a higher rate than control muscles over the first 45 min of the fatigue protocol. When glycolysis was inhibited with sodium iodoacetate, fatigability was not influenced by the addition of a CA inhibitor. These results further support the existence of a link between CA III activity and energy metabolism in type I skeletal muscle fibers.Key words: muscle fatigue, sulfonamide, glycolysis, glycogenolysis, soleus muscle, glycogen, phosphorylase.

scholarly journals MyoD-positive myoblasts are present in mature fetal organs lacking skeletal muscle

2001 ◽  
Vol 155 (3) ◽  
pp. 381-392 ◽  
Author(s):  
Jacquelyn Gerhart ◽  
Brian Bast ◽  
Christine Neely ◽  
Stephanie Iem ◽  
Paula Amegbe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Rt Pcr ◽  
Skeletal Myoblasts ◽  
In Situ Hybridizations ◽  
Fetal Organs ◽  
The Brain

The epiblast of the chick embryo gives rise to the ectoderm, mesoderm, and endoderm during gastrulation. Previous studies revealed that MyoD-positive cells were present throughout the epiblast, suggesting that skeletal muscle precursors would become incorporated into all three germ layers. The focus of the present study was to examine a variety of organs from the chicken fetus for the presence of myogenic cells. RT-PCR and in situ hybridizations demonstrated that MyoD-positive cells were present in the brain, lung, intestine, kidney, spleen, heart, and liver. When these organs were dissociated and placed in culture, a subpopulation of cells differentiated into skeletal muscle. The G8 antibody was used to label those cells that expressed MyoD in vivo and to follow their fate in vitro. Most, if not all, of the muscle that formed in culture arose from cells that expressed MyoD and G8 in vivo. Practically all of the G8-positive cells from the intestine differentiated after purification by FACS®. This population of ectopically located cells appears to be distinct from multipotential stem cells and myofibroblasts. They closely resemble quiescent, stably programmed skeletal myoblasts with the capacity to differentiate when placed in a permissive environment.

Lineage restriction of the myogenic conversion factor myf-5 in the brain

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4077-4083 ◽  
Author(s):  
S. Tajbakhsh ◽  
M.E. Buckingham
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Conversion Factor ◽  
Embryonic Stem ◽  
Posterior Hypothalamus ◽  
Myogenic Lineage ◽  
Myogenic Factor ◽  
The Brain

myf-5 is one of four transcription factors belonging to the MyoD family that play key roles in skeletal muscle determination and differentiation. We have shown earlier by gene targeting nlacZ into the murine myf-5 locus that myf-5 expression in the developing mouse embryo is closely associated with the restriction of precursor muscle cells to the myogenic lineage. We now identify unexpected expression of this myogenic factor in subdomains of the brain. myf-5 expression begins to be detected at embryonic day 8 (E8) in the mesencephalon and coincides with the appearance of the first differentiated neurons; expression in the secondary prosencephalon initiates at E10 and is confined to the ventral domain of prosomere p4, later becoming restricted to the posterior hypothalamus. This expression is observed throughout embryogenesis. No other member of the MyoD family is detected in these regions, consistent with the lack of myogenic conversion. Furthermore, embryonic stem cells expressing the myf-5/nlacZ allele yield both skeletal muscle and neuronal cells when differentiated in vitro. These observations raise questions about the role of myf-5 in neurogenesis as well as myogenesis, and introduce a new lineage marker for the developing brain.

scholarly journals McArdle Disease: New Insights into Its Underlying Molecular Mechanisms

2019 ◽  
Vol 20 (23) ◽  
pp. 5919
Author(s):  
Llavero ◽  
Arrazola Sastre ◽  
Luque Montoro ◽  
Gálvez ◽  
Lacerda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Phosphorylase ◽  
Molecular Mechanisms ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
High Serum ◽  
Creatine Kinase Activity ◽  
Exercise Intolerance ◽  
Mcardle Disease ◽  
Type V

McArdle disease, also known as glycogen storage disease type V (GSDV), is characterized by exercise intolerance, the second wind phenomenon, and high serum creatine kinase activity. Here, we recapitulate PYGM mutations in the population responsible for this disease. Traditionally, McArdle disease has been considered a metabolic myopathy caused by the lack of expression of the muscle isoform of the glycogen phosphorylase (PYGM). However, recent findings challenge this view, since it has been shown that PYGM is present in other tissues than the skeletal muscle. We review the latest studies about the molecular mechanism involved in glycogen phosphorylase activity regulation. Further, we summarize the expression and functional significance of PYGM in other tissues than skeletal muscle both in health and McArdle disease. Furthermore, we examine the different animal models that have served as the knowledge base for better understanding of McArdle disease. Finally, we give an overview of the latest state-of-the-art clinical trials currently being carried out and present an updated view of the current therapies.

Sign in / Sign up

Export Citation Format

Share Document