Defective oxidative metabolism of myodystrophic skeletal muscle mitochondria

Lee, C. P.; Martens, Margaret E.; Jankulovska, L; Neymark, Michael A.

doi:10.1002/mus.880020504

Cited by 28 publications

(8 citation statements)

References 41 publications

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“…An open biopsy ofthe rectus femoris muscle was performed under local anesthesia for histopathological and biochemical determinations. Portions of the biopsy were frozen in liquid nitrogen-cooled Freon for histochemistry, fixed in 2% glutaraldehyde, 2% paraformaldehyde for electron microscopy and x-ray microanalysis, frozen in liquid nitrogen for subsequent biochemical assays, and used for preparation of fresh skeletal muscle mitochondrial fractions for oxygen electrode and cytochrome determinations (9,10). The remainder of the mitochondrial fraction was frozen for assay of selected mitochondrial enzymes.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Haller¹,

Henriksson²,

Jorfeldt³

et al. 1991

J. Clin. Invest.

123

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We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39±5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (V02) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v 02 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7±2.1) despite normal oxygen carrying capacity and Hgb-02 PSO. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Q..: patient = 303 ml/min per kg, normal men 238±36) and the slope of increase in Q relative to V02 (i.e., A&Q/AVO2) from rest to exercise was exaggerated (A&Q/AVO2, patient = 29, normal men = 4.7±0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex H in skeletal muscle was confirmed by the finding ofdeficiency ofsuccinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle. (J. Clin.

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Section: Discussionmentioning

confidence: 99%

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Haller¹,

Henriksson²,

Jorfeldt³

et al. 1991

J. Clin. Invest.

123

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“…All procedures for mitochondrial isolation were conducted at 4 °C. Mitochondria were isolated from skeletal muscle essentially as described by Lee et al . (1979).…”

Section: Methodsmentioning

confidence: 99%

Free radical generation by skeletal muscle of adult and old mice: effect of contractile activity

Vasilaki

Mansouri²,

Remmen³

et al. 2006

Aging Cell

183

190

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SummaryOxidative modification of cellular components may contribute to tissue dysfunction during aging. In skeletal muscle, contractile activity increases the generation of reactive oxygen and nitrogen species (ROS). The question of whether contraction-induced ROS generation is further increased in skeletal muscle of the elderly is important since this influences recommendations on their exercise participation. Three different approaches were used to examine whether aging influences contraction-induced ROS generation. Hind limb muscles of adult and old mice underwent a 15-min period of isometric contractions and we examined ROS generation by isolated skeletal muscle mitochondria, ROS release into the muscle extracellular fluid using microdialysis techniques, and the muscle glutathione and protein thiol contents. Resting skeletal muscle of old mice compared with adult mice showed increased ROS release from isolated mitochondria, but no changes in the extracellular levels of superoxide, nitric oxide, hydrogen peroxide, hydroxyl radical activity or muscle glutathione and protein thiol contents. Skeletal muscle mitochondria isolated from both adult and old mice after contractile activity showed significant increases in hydrogen peroxide release compared with precontraction values. Contractions increased extracellular hydroxyl radical activity in adult and old mice, but had no significant effect on extracellular hydrogen peroxide or nitric oxide in either group. In adult mice only, contractile activity increased the skeletal muscle release of superoxide. A similar decrease in muscle glutathione and protein thiol contents was seen in adult and old mice following contractions. Thus, contractile activity increased skeletal muscle ROS generation in both adult and old mice with no evidence for an age-related exacerbation of ROS generation.

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“…Mitochondrial preparations have been isolated from both fresh [6][7][8][9][10][11] and frozen [8,10] skeletal muscle. Fresh tissue is essential for isolation of intact mitochondria.…”

Section: Systematic Approaches To the Study Of Mitochondrial Electronmentioning

confidence: 99%

Defective oxidative metabolism of myodystrophic skeletal muscle mitochondria

Cited by 28 publications

References 41 publications

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Free radical generation by skeletal muscle of adult and old mice: effect of contractile activity

Use of isolated mitochondria as a tool for biochemical characterization of neuromuscular disorders

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