Successful treatment of murine muscular dystrophy with the protease inhibitor bestatin

Tsuji, Shigekatsu; Matsushita, Hiroshi

doi:10.1016/0022-510x(86)90006-7

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…In the dy/dy mouse, the muscle initially appears normal, with normal fiber-type differentiation up to 2 wk of age, when the necrotic process starts. After 1 mo of age, there is marked variation in fiber size with necrotic and regenerating fibers (30). Interstitial fibrosis becomes evident as the disease progresses.…”

mentioning

confidence: 99%

Selected Contribution: Merosin deficiency leads to alterations in passive and active skeletal muscle mechanics

Jannapureddy

Patel

Hwang

et al. 2003

Journal of Applied Physiology

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The role of extracellular elements on the mechanical properties of skeletal muscles is unknown. Merosin is an essential extracellular matrix protein that forms a mechanical junction between the sarcolemma and collagen. Therefore, it is possible that merosin plays a role in force transmission between muscle fibers and collagen. We hypothesized that deficiency in merosin may alter passive muscle stiffness, viscoelastic properties, and contractile muscle force in skeletal muscles. We used the dy/dy mouse, a merosin-deficient mouse model, to examine changes in passive and active muscle mechanics. After mice were anesthetized and the diaphragm or the biceps femoris hindlimb muscle was excised, passive length-tension relationships, stress-relaxation curves, or isometric contractile properties were determined with an in vitro biaxial mechanical testing apparatus. Compared with controls, extensibility was smaller in the muscle fiber direction and the transverse fiber direction of the mutant mice. The relaxed elastic modulus was smaller in merosin-deficient diaphragms compared with controls. Interestingly, maximal muscle tetanic stress was depressed in muscles from the mutant mice during uniaxial loading but not during biaxial loading. However, presence of transverse passive stretch increases maximal contractile stress in both the mutant and normal mice. Our data suggest that merosin contributes to muscle passive stiffness, viscoelasticity, and contractility and that the mechanism by which force is transmitted between adjacent myofibers via merosin possibly in shear.

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confidence: 99%

Selected Contribution: Merosin deficiency leads to alterations in passive and active skeletal muscle mechanics

Jannapureddy

Patel

Hwang

et al. 2003

Journal of Applied Physiology

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“…When we consider bestatin as a therapeutic agent for muscular dystrophies, it is important to note that bestatin has a membrane stabilizing action in addition to its previously proposed effect as a protease inhibitor. 12 The amount of bestatin that has been used for the dy/dy mice is 0.4mg/day,12 which corresponds to half of our dose for the mdx mice. The dosage of lOOmg/kg body weight/day used in our study was a relatively large amount.…”

Section: Discussionmentioning

confidence: 99%

The Stabilizing Effect of Bestatin on the Resting Membrane Potentials of X‐Linked Muscular Dystrophy Mice

Kusumoto

Kurihara

Hidaka

et al. 1990

Psychiatry Clin Neurosci

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The resting membrane potentials of X‐linked muscular dystrophy (mdx) mice are about 10 mV lower than those of control (C57BL/10Sc) mice. Also repetitive action potentials which resemble insertion myotonia are frequently recorded intracellularly from the mdx mice of various ages. When the mdx mice are treated with bestatin intraperito‐neally for 7 days, the RMPs improvement almost attained its normal levels. Repetitive action potential bursts (electrical myotonia) recorded at the time of microelectrode insertion had decreased or abolished after bestatin therapy. Another set of in vitro experiments to see direct action of bestatin to the hemidiaphragm preparations of the mdx mice reveal improvement in RMP's and a reduction in electrical myotonia within a 30‐minute exposure to Tyrode's solution with bestatin. Bestatin has a favorable direct effect on the muscle fiber membrane to stabilize RMP's and suppress muscle membrane irritability.

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“…It can also enhance the G-and GM-CSF-induced colony formation to modulate the proliferation and differentiation of human bone marrow cells [10,11]. Because of these significant therapeutic activities, bestatin has been studied as a therapeutic drug for cancer, resistant infection, muscular dystrophy [12], myelodysplastic syndrome and chronic leukemia [13].…”

Section: Introductionmentioning

confidence: 98%

Development of a liquid chromatography/tandem mass spectrometry assay for the determination of bestatin in rat plasma and its application to a pharmacokinetic study

Wang

Fan

Chen

et al. 2007

Journal of Chromatography B

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Successful treatment of murine muscular dystrophy with the protease inhibitor bestatin

Cited by 7 publications

References 23 publications

Selected Contribution: Merosin deficiency leads to alterations in passive and active skeletal muscle mechanics

Selected Contribution: Merosin deficiency leads to alterations in passive and active skeletal muscle mechanics

The Stabilizing Effect of Bestatin on the Resting Membrane Potentials of X‐Linked Muscular Dystrophy Mice

Development of a liquid chromatography/tandem mass spectrometry assay for the determination of bestatin in rat plasma and its application to a pharmacokinetic study

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