Oxyradical Damage and Mitochondrial Enzyme Activities in the mdx Mouse

Hauser, Erwin; Höger, Harald; Bittner, Reginald E.; Widhalm, K.; Herkner, Kurt; Lubec, Gert

doi:10.1055/s-2007-979768

Cited by 49 publications

(32 citation statements)

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“…In control mice, the association between enhanced muscle-fiber SDH activity and improved fatigue resistance following IGF-I administration (in the EDL muscle) was less clear, indicating that other mechanisms may be responsible for this growth factor-mediated effect in normal (nonpathological) muscle. We found that median fiber SDH activity was lower in the skeletal muscles of mdx compared with control mice, a finding in general agreement with that of Dunn and colleagues 14 but different from others who have found either no difference 34 or higher activity 23 in muscles from mdx than control mice. These discrepancies are likely due to methodological differences between the studies.…”

Section: Discussionsupporting

confidence: 88%

“…However, it is unclear whether the oxidative capacity of limb skeletal muscles of dystrophic mdx mice differs from that in wild-type control mice. There have been reports that SDH activity in skeletal muscles of such mice is lower, 14 higher, 23 or not different 34 from that in muscles from control (C57BL/10) mice. Therefore, one aim of the present study was to determine whether a difference existed in SDH activity in extensor digitorum longus (EDL) and soleus muscles between mdx and control mice and whether muscle fatigue was influenced by SDH activity.…”

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confidence: 90%

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Administration of insulin‐like growth factor‐I improves fatigue resistance of skeletal muscles from dystrophic mdx mice

2004

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Muscle fatigue occurs in many neuromuscular diseases, including the muscular dystrophies, and it contributes to a loss of functional capacity and reduced quality of life for affected patients. An improvement in fatigue resistance has been observed in diaphragm muscles of mdx mice following insulin-like growth factor-I (IGF-I) administration. Whether similar treatment can improve locomotor muscle function in mdx mice is not known. We examined the efficacy of IGF-I administration (1 mg/kg daily s.c. for 8 weeks) on structural, metabolic, and functional properties of extensor digitorum longus (EDL) and soleus muscles of mdx mice, and tested the hypothesis that IGF-I treatment would improve function in these muscles. After treatment, muscles were more resistant to fatigue during repeated maximal contractions than muscles from untreated mice, an improvement associated with increased muscle fiber succinate dehydrogenase activity in the absence of changes in cellular (single-fiber) contractile activation characteristics. The findings have important clinical implications, not just for the dystrophinopathies, but for all neuromuscular pathologies where fatigue of locomotor muscles limits functional capacity and decreases quality of life.

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Section: Discussionsupporting

confidence: 88%

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confidence: 90%

Administration of insulin‐like growth factor‐I improves fatigue resistance of skeletal muscles from dystrophic mdx mice

2004

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“…This quantitative histochemical method offers more precise informations on the activities and amounts of enzymes in each cell type than a biochemical method using homogenates. Our findings with this approach differ to some extent from those obtained by Dunn et al (1993) and Hauser et al (1995). We found absence of dystrophin has no effects on the activities of either SDH or LDH in muscle fibres of adult mdx gastrocnemius.…”

Section: Introductioncontrasting

confidence: 99%

“…Previously, Dunn et al (1993) reported that SDH activity determined biochemically in homogenates of hind limb muscles isolated from adult mdx mice was significantly lower than that of corresponding C57BL/10 control muscles but the activities of several glycolytic enzymes, including LDH, were similar in mdx and control muscle homogenates. In contrast, using a similar biochemical method, Hauser et al (1995) showed that SDH activity is significantly elevated in hind limb muscles of adult mdx mouse compared to normal controls. Such equivocal reports may be due to the different proportions of heterogeneous cells present in skeletal muscles and which vary with age and from muscle to muscle.…”

Section: Introductionmentioning

confidence: 81%

“…In contrast, Hauser et al (1995) reported that a homogenate of gastrocnemius and quadriceps femoris muscles of 10-week-old mdx mouse had elevated activities of several mitochondrial enzymes, such as succinate:phenazine methosulphate oxidoreductase, NADH:O 2 oxidoreductase and cytochrome c oxidase, compared with those of C57BL/10 control muscles. Our results for LDH activity in gastrocnemius muscle fibres of 10-week-old mdx mouse agree with those of Dunn et al (1993), but for SDH activity they disagree with those of both Dunn et al (1993) and Hauser et al (1995). A possible reason for this disagreement is that the proportions of the number of each fibre type present in mdx muscles differ from those in C57BL/10 control muscles (Carnwath and Shotton 1987).…”

Section: Time Courses Of the Enzyme Reactionsmentioning

confidence: 89%

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Localisation and quantification of dehydrogenase activities in single muscle fibres of mdx gastrocnemius

et al. 1999

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The kinetics of succinate (SDH) and lactate (LDH) dehydrogenases were determined in single muscle fibres in unfixed sections of the gastrocnemius of dystrophic mdx mice (with an X-linked genetic disorder lacking a cytoskeletal protein, dystrophin) and agematched C57BL/10 control mice. Quantitative gel substrate-film techniques and a real-time image analysis system were used. Three main fibre types were observed in regenerated mdx gastrocnemius and in corresponding controls: small fibres (S) with high SDH and LDH initial reaction velocities and activities, large fibres (L) with low activities of these dehydrogenases and intermediatesized fibres (I) with intermediate enzyme activities. The small and intermediate fibres in both mdx and control muscles exhibited respectively high and moderate subsarcolemmal SDH and LDH activities attributable to accumulated mitochondria. The ratios of the initial velocities of the intrinsic enzyme reactions in the sarcoplasm, excluding the subsarcolemmal regions, of mdx muscle fibres compared to those in control fibres were 0.958 (S), 1.09 (I) and 0.959 (L) for SDH, and 1.03 (S), 1.06 (I) and 1.07 (L) for LDH. A parameter a, a measure of the diffusion of LDH out of muscle sections during incubation on gel substrate films, was found to be 0.981 and 1.00 in mdx and control muscles, respectively. Thus there are no significant differences in the activities and microenvironments of the enzymes between regenerated mdx muscle fibres and normal control muscle fibres. These data suggest that dystrophin deficiency in mdx muscles has no effects on the interactions of LDH with cytoskeletal proteins or on SDH activities in mitochondria whose number and morphology differ in mdx muscle fibres compared to those in normal controls. SDH and LDH activities were also found in the mitochondria clustered on two longitudinally directed poles of each central nucleus in regenerated mdx muscle fibres. They were proportional to the activities in the sarcoplasm excluding the subsarcolemmal regions.

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