scholarly journals Increased muscle calcium A possible cause of mitochondrial dysfunction and cellular necrosis in denervated rat skeletal muscle

1981 ◽  
Vol 196 (3) ◽  
pp. 663-667 ◽  
Author(s):  
M Joffe ◽  
N Savage ◽  
H Isaacs
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Causal Relationship ◽  
Cell Necrosis ◽  
Rat Skeletal Muscle ◽  
Mitochondrial Fractions ◽  
Cellular Necrosis ◽  
And Control ◽  
Muscle Calcium ◽  
Possible Cause

Mitochondrial preparations derived from denervated rat skeletal muscle and paired controls were characterized with respect to their ability to take up externally added Ca2+. The denervated and control muscle homogenates and mitochondrial [Ca2+] were also determined. Our data indicate that the denervated mitochondria are able to take up less Ca2+ than the controls before uncoupling occurs. This defect is associated with elevated [Ca2+] in homogenate and mitochondrial fractions in the denervated state. The causal relationship between Ca2+ overload, mitochondrial functional damage and cell necrosis is discussed.

Regulation of CPT I activity in intermyofibrillar and subsarcolemmal mitochondria from human and rat skeletal muscle

2004 ◽  
Vol 286 (1) ◽  
pp. E85-E91 ◽  
Author(s):  
Veronic Bezaire ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Moderate Intensity ◽  
Rat Skeletal Muscle ◽  
Moderate Intensity Exercise ◽  
Mitochondrial Fractions ◽  
Decreasing Ph ◽  
Subsarcolemmal Mitochondria ◽  
Cpt I

Carnitine palmitoyltransferase I (CPT I) is considered the rate-limiting enzyme in the transfer of long-chain fatty acids (LCFA) into the mitochondria and is reversibly inhibited by malonyl-CoA (M-CoA) in vitro. In rat skeletal muscle, M-CoA levels decrease during exercise, releasing the inhibition of CPT I and increasing LCFA oxidation. However, in human skeletal muscle, M-CoA levels do not change during moderate-intensity exercise despite large increases in fat oxidation, suggesting that M-CoA is not the sole regulator of increased CPT I activity during exercise. In the present study, we measured CPT I activity in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondria isolated from human vastus lateralis (VL), rat soleus (Sol), and red gastrocnemius (RG) muscles. We tested whether exercise-related levels (∼65% maximal O2 uptake) of calcium and adenylate charge metabolites (free AMP, ADP, and Pi) could override the M-CoA-induced inhibition of CPT I activity and explain the increased CPT I flux during exercise. Protein content was ∼25-40% higher in IMF than in SS mitochondria in all muscles. Maximal CPT I activity was similar in IMF and SS mitochondria in all muscles (VL: 282 ± 46 vs. 280 ± 51; Sol: 390 ± 81 vs. 368 ± 82; RG: 252 ± 71 vs. 278 ± 44 nmol·min-1·mg protein-1). Sensitivity to M-CoA did not differ between IMF and SS mitochondria in all muscles (25-31% inhibition in VL, 52-70% in Sol and RG). Calcium and adenylate charge metabolites did not override the M-CoA-induced inhibition of CPT I activity in mitochondria isolated from VL, Sol, and RG muscles. Decreasing pH from 7.1 to 6.8 reduced CPT I activity by ∼34-40% in both VL mitochondrial fractions. In summary, this study reports no differences in CPT I activity or sensitivity to M-CoA between IMF and SS mitochondria isolated from human and rat skeletal muscles. Exercise-induced increases in calcium and adenylate charge metabolites do not appear responsible for upregulating CPT I activity in human or rat skeletal muscle during moderate aerobic exercise.

scholarly journals PGC-1β prevents statin-associated myotoxicity in oxidative skeletal muscle

2017 ◽  
Author(s):  
François Singh ◽  
Joffrey Zoll ◽  
Urs Duthaler ◽  
Anne-Laure Charles ◽  
Gilles Laverny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Rat Skeletal Muscle ◽  
Oxidative Defense ◽  
Muscle Types ◽  
And Function

AbstractStatins are generally well-tolerated, but can induce myopathy. Statins are associated with impaired expression of PGC-1β in human and rat skeletal muscle. The current study was performed to investigate the relation between PGC-1β expression and function and statin-associated myopathy. In WT mice, atorvastatin impaired mitochondrial function in glycolytic, but not in oxidative muscle. In PGC-1β KO mice, atorvastatin induced a shift from oxidative type IIA to glycolytic type IIB myofibers mainly in oxidative muscle and mitochondrial dysfunction was observed in both muscle types. In glycolytic muscle of WT and KO mice and in oxidative muscle of KO mice, atorvastatin suppressed mitochondrial proliferation and oxidative defense, leading to apoptosis. In contrast, mitochondrial function was maintained or improved and apoptosis decreased by atorvastatin in oxidative muscle of WT mice. In conclusion, PGC-1β has an important role in preventing damage to oxidative muscle in the presence of a mitochondrial toxicant such as atorvastatin.

Fiber type-related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone

2006 ◽  
Vol 21 (2) ◽  
pp. 372-380 ◽  
Author(s):  
Bodvael Fraysse ◽  
Jean-François Desaphy ◽  
Jean-François Rolland ◽  
Sabata Pierno ◽  
Antonella Liantonio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Calcium Homeostasis ◽  
Fiber Type ◽  
Rat Skeletal Muscle ◽  
Muscle Calcium

scholarly journals Unmasking Potential Intracellular Roles For Dysferlin through Improved Immunolabeling Methods

2011 ◽  
Vol 59 (11) ◽  
pp. 964-975 ◽  
Author(s):  
Joseph A. Roche ◽  
Lisa W. Ru ◽  
Andrea M. O’Neill ◽  
Wendy G. Resneck ◽  
Richard M. Lovering ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Potential Role ◽  
Human Muscle ◽  
Rat Skeletal Muscle ◽  
Mouse Muscle ◽  
Contraction Coupling ◽  
Dihydropyridine Receptors ◽  
And Control ◽  
Muscle Biopsies

Mutations in the DYSF gene that severely reduce the levels of the protein dysferlin are implicated in muscle-wasting syndromes known as dysferlinopathies. Although studies of its function in skeletal muscle have focused on its potential role in repairing the plasma membrane, dysferlin has also been found, albeit inconsistently, in the sarcoplasm of muscle fibers. The aim of this article is to study the localization of dysferlin in skeletal muscle through optimized immunolabeling methods. We studied the localization of dysferlin in control rat skeletal muscle using several different methods of tissue collection and subsequent immunolabeling. We then applied our optimized immunolabeling methods on human cadaveric muscle, control and dystrophic human muscle biopsies, and control and dysferlin-deficient mouse muscle. Our data suggest that dysferlin is present in a reticulum of the sarcoplasm, similar but not identical to those containing the dihydropyridine receptors and distinct from the distribution of the sarcolemmal protein dystrophin. Our data illustrate the importance of tissue fixation and antigen unmasking for proper immunolocalization of dysferlin. They suggest that dysferlin has an important function in the internal membrane systems of skeletal muscle, involved in calcium homeostasis and excitation-contraction coupling.

Effect of thyroid status on K+-stimulated metabolism and 45Ca exchange in rat skeletal muscle

1984 ◽  
Vol 247 (4) ◽  
pp. E421-E430 ◽  
Author(s):  
C. Van Hardeveld ◽  
T. Clausen
Keyword(s):  
Skeletal Muscle ◽  
Extensor Digitorum Longus ◽  
Lactate Production ◽  
Metabolic Effects ◽  
Rat Skeletal Muscle ◽  
Thyroid Status ◽  
High K ◽  
Muscle Calcium ◽  
45Ca Efflux ◽  
K Release

In the perfused hindlimbs of hypo-, eu-, and hyperthyroid rats, high K+o (20 mM) markedly stimulated glucose uptake, lactate production, and O2-consumption to levels increasing with the thyroid status. At Ca2o+ less than 50 microM, all the responses became transient. In the hypothyroid preparations, caffeine (5 mM) produced no stimulation, but in those obtained from eu- and hyperthyroid rats, it increased all the metabolic parameters as well as K+ release in proportion to thyroid status. In isolated soleus and extensor digitorum longus muscles, both high K+o and caffeine stimulated 45Ca-efflux, with the response increasing in proportion to thyroid status. This stimulation was reduced by 70-100% with dantrolene (10(-5) M), which in earlier studies was shown to suppress the metabolic effects of high K+o and caffeine. High K+o also increased 45Ca-influx but produced no change in muscle calcium contents. The results support the idea that thyroid hormones control substrates availability and energy consumption in skeletal muscle by increasing the amount of sarcoplasmic reticulum and thereby the rate of Ca2+ mobilization into the cytosol.

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