Energy Metabolism of the Skeletal Muscle of Genetically Dystrophic Hamster

Dhalla, Naranjan S.; Fedelesová, M; Toffler, Ivan

doi:10.1139/o72-076

Cited by 27 publications

(6 citation statements)

References 4 publications

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“…Indeed, alterations in the respiratory and phosphorylation activities of mitochondria from other models of muscular dystrophy have also been reported in the literature (Lochner & Brink, 1967;Wrogemann, Jacobson & Blanchaer, 1973). Such changes in mitochondrial functions may be partly responsible for metabolic disturbance and malfunction of the dystrophic muscle (Dhalla, Fedelesova & Toffler, 1972).…”

Section: Discussionmentioning

confidence: 77%

Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster

et al. 1975

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1. The function of mitochondria, sarcotubular membranes (heavy microsomes), sarcolemma and myofibrils from the hind-leg skeletal muscle of about 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters was examined. 2. The mitochondrial calcium uptake as well as mitochondrial phosphorylation and respiratory rates were lower in 60-day-old myopathic skeletal muscle, unlike 150-day-old myopathic animals, when pyruvate-malate and glutamate-malate were used as substrates. However, mitochondria from 150-day-old myopathic animals showed depressed glutamate-dependent respiratory and phosphorylation rates and succinate-supported initial rate of calcium uptake. 3. The microsomal calcium-uptake, but not calcium-binding, and Ca2+-stimulated adenosine triphosphatase (ATPase) activity of the 150-day-old myopathic skeletal muscle were lower than the control values. Although microsomal calcium-binding, calcium-uptake and ATPase activities of the 60-day-old myopathic muscle were not depressed significantly, the initial rate of calcium uptake was less than the control. 4. The sarcolemmal Ca2+-ATPase, but not Mg2+-ATPase or Na+ +K+-ATPase, activity was higher in 60-day-old myopathic muscle whereas the activities of all these enzymes from 150-day-old myopathic animals were higher than the control. On the other hand, the Na+ +K+-ATPase activities from 60- and 150-day-old myopathic animals were inhibited by ouabain to a lesser extent in comparison with the respective control values. 5. The myofibrillar Ca2+-ATPase and Mg2+-ATPase activities as well as inhibition of Mg2+-ATPase due to Na+ and K+ in myopathic muscle were no different from the control values. 6. The results reported here give further support to the view that different membrane systems of the dystrophic muscle are defective.

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Section: Discussionmentioning

confidence: 77%

Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster

et al. 1975

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“…Different mechanisms including impaired metabolism [8,[26][27][28][29][30][31], structural and biochemical membrane defects [32][33][34][35][36][37][38][39] and Ca 2+ regulatory abnormalities [40][41][42][43][44][45][46][47][48][49][50][51][52] have been described to understand the pathogenesis of weakness in dystrophic muscle. An increased activity of enzymes, such as CK in the serum is considered to reflect damage to the muscle cell membrane and serves as a sensitive marker for the progression of this disease [53][54][55][56][57][58][59].…”

Section: Biochemical Defects In Dystrophic Musclementioning

confidence: 99%

“…Furthermore, derangements in the function of intracellular membrane systems such as the sarcoplasmic reticulum (SR) [40,76,88] and mitochondria [41,76,[94][95][96] were reported in dystrophic muscle. Although no alterations in myofibrillar ATPase activity and contractile proteins in myopathic hamster muscle were observed [30,76], some investigators have shown defective myosin in a chicken model of muscular dystrophy [97]. Nonetheless, marked changes in metabolism [26][27][28][29][30]98] indicating the impaired performance of skeletal muscle in different types of muscle disorders may be associated with subcellular defects and metabolic abnormalities.…”

Section: Biochemical Defects In Dystrophic Musclementioning

confidence: 99%

“…Although no alterations in myofibrillar ATPase activity and contractile proteins in myopathic hamster muscle were observed [30,76], some investigators have shown defective myosin in a chicken model of muscular dystrophy [97]. Nonetheless, marked changes in metabolism [26][27][28][29][30]98] indicating the impaired performance of skeletal muscle in different types of muscle disorders may be associated with subcellular defects and metabolic abnormalities. In addition, maldistribution of electrolytes in dystrophic myocytes [66,77], there occurs the development of intracellular Ca 2+ -overload [41][42][43][44]99], which activates different proteolytic enzymes [100,101] and leads to muscle breakdown as well as structural defects dystrophic muscle of DMD patients [102,103].…”

Section: Biochemical Defects In Dystrophic Musclementioning

confidence: 99%

“…In order to examine the functional significance of metabolic and subcellular alterations for impaired performance of myopathic muscle, hind leg muscles from two experimental models (BIO 14.6 and UM-X7.1) of Syrian hamster (δ-sarcoglycanopathy) at different stages of development were used [30,40,[74][75][76]. It may be noted that the clinical signs of muscle impairment in BIO 14.6 strain of hamsters start developing at the age of 100 to 150 days (early stage) whereas moderate and severe stages of myopathy become apparent at 180-210 days and 260-275 days of age, respectively [30,146]. On the other hand, UM-X7.1 strain of myopathic hamsters develop degenerative lesions as early as 20 to 30 days whereas these animals at the age of about 60 days and about 150 days were considered to be at moderate and severe stages of muscular disorder, respectively [74,147].…”

Section: Metabolic and Subcellular Defects In Skeletal Muscle Of Myopathic Hamstermentioning

confidence: 99%

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Role of molecular and metabolic defects in impaired performance of dystrophic skeletal muscles

Bhullar¹,

Nusier²,

Shah³

et al. 2021

J. Mol. Clin. Med.

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There occurs a progressive weakness and wastage of skeletal muscle in different types of muscular dystrophy. The loss of muscle fibers in dystrophic muscle with impaired function is associated with leakage of intracellular enzymes, maldistribution of electrolyte content and metabolic defects in myocytes. Marked increases in the sarcolemma (SL) Na+-K+ ATPase and Ca2+/Mg2+-ecto ATPase activities, as well as depressions in the sarcoplasmic reticulum (SR) Ca2+-uptake and Ca2+-pump ATPase activities were seen in dystrophic muscles of a hamster model of myopathy. In addition, impaired mitochondrial oxidative phosphorylation and decrease in the high energy stores as a consequence of mitochondrial Ca2+-overload were observed in these myopathic hamsters. In some forms of muscular dystrophy, it has been shown that deficiency of dystrophin produces marked alterations in the SL permeability and promotes the occurrence of intracellular Ca2+-overload for inducing metabolic defects, activation of proteases and contractile abnormalities in dystrophic muscle. Increases in SR Ca2+-release channels, SL Na+-Ca2+ exchanger and SL store-operated Ca2+-channels have been reported to induce Ca2+-handling abnormalities in a mouse model of muscular dystrophy. Furthermore, alterations in lipid metabolism and development of oxidative stress have been suggested as mechanisms for subcellular remodeling and cellular damage in dystrophic muscle. Although, several therapeutic interventions including gene therapy are available, these treatments neither fully prevent the course of development of muscular disorder nor fully improve the function of dystrophic muscle. Thus, extensive reasearch work with some novel inhibitors of oxidative stress, SL Ca2+-entry systems such as store-operated Ca2+-channels, Na+-Ca2+ exchanger and Ca2+/Mg2+-ecto ATPase (Ca2+-gating mechanism), as well as SR Ca2+-release and Ca2+-pump systems needs to be carried out in combination of gene therapy for improved beneficial effects in muscular dystrophy.

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Structural changes in myosin during contraction and the state of ATP in the intact frog muscle

Bárány

Burt

et al. 1975

J Supramol Struct

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The reactivity of myosin to [14C]-labeled N-ethylmaleimide ([14C]NEM) or to tritium was determined in functionally different frog muscles. The incorporation of [14C]NEM into myosin decreased during isotonic or isometric contractions, as compared to resting muscle. The cysteine residues which were protected during contraction were not involved in the ATPase activity or the actin-binding ability of myosin. Peptide mapping revealed that several residues were protected simultaneously. The incorporation of tritium into the peptide N-H groups of myosin was also decreased during muscle activity. These data support the idea that activation and subsequent contraction of muscle are correlated with structural changes in the myosin molecule. The reactivity of myosin to [14C]NEM was increased when the muscle was stretched to 140% rest length and treated with iodoacetate to deplete ATP. Based on in vitro experiments and on literature data, it is suggested that in the resting muscle myosin contains bound MgATP which decreases the rate of incorporation of [14C]NEM into myosin and that upon the irreversible loss of ATP the rate increases. 31P nuclear magnetic resonance signals from a number of phosphates were detected in the intact frog muscle. The data indicated that the minimum concentration of ATP in the muscle is 3 mM, a value which agrees with that of chemical determination. The characteristic chemical shifts, coupling constants, and line widths of ATP in the muscle were considerably altered from that of either free ATP in aqueous solutions or ATP in perchloric acid extracts of muscle.

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Energy Metabolism of the Skeletal Muscle of Genetically Dystrophic Hamster

Cited by 27 publications

References 4 publications

Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster

Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster

Role of molecular and metabolic defects in impaired performance of dystrophic skeletal muscles

Structural changes in myosin during contraction and the state of ATP in the intact frog muscle

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