Serum Transaminase Levels in Boys With Duchenne and Becker Muscular Dystrophy

McMillan, Hugh J.; Gregas, Matt; Darras, Basil T.; Kang, Peter B.

doi:10.1542/peds.2010-0929

Cited by 76 publications

(64 citation statements)

References 13 publications

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“…Findings in humans and in animal models point to disruption of the sarcolemma as a main cause of neuromuscular disease (Mendell et al 1995;Straub et al 1997). Consistent with this, patients affected by Duchenne type neuromuscular dystrophy exhibit increased plasma levels of some muscle fiber content, including enzymes (McMillan et al 2011) and growth factors (D'Amore et al 1994). Of note with respect to our findings, it has been reported that patients affected by painful neuromuscular diseases such as polymyositis and Duchenne type neuromuscular dystrophy exhibit increased expression of GDNF in regenerating muscle fibers (Suzuki et al 1998a).…”

Section: Fig 2 Gdnf Produces Mechanical Hyperalgesia and Sensitizesmentioning

confidence: 61%

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

Álvarez

Chen

Bogen

et al. 2012

Journal of Neurophysiology

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Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E(2) at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (<4 h; hyperalgesic priming). Selective neurotoxic destruction of IB4(+) nociceptors attenuated both GDNF hyperalgesia and hyperalgesic priming. Ergonomic muscular injury induced by eccentric exercise or mechanical vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.

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Section: Fig 2 Gdnf Produces Mechanical Hyperalgesia and Sensitizesmentioning

confidence: 61%

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

Álvarez

Chen

Bogen

et al. 2012

Journal of Neurophysiology

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“…Although very large elevations in serum ALT are generally believed to be liver‐specific, ALT elevations are also noted following strenuous exercise and in patients with muscle diseases such as muscular dystrophy . A biomarker with greater liver specificity could be valuable in the clinic when the source of an ALT elevation is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Candidate biomarkers for the diagnosis and prognosis of drug‐induced liver injury: An international collaborative effort

et al. 2018

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“…Dysregulated serum biomarkers, such as CK and alanine transaminase (ALT), are hallmarks of dystrophic muscle and are often used to diagnose the severity of muscle disease in both humans and mice (23,(42)(43)(44). We next measured the levels of serum CK in adult WT, Tg(Cmk-Mir486), Dmd mdx-5Cv , and Dmd mdx-5Cv Tg(Cmk-Mir486) mice.…”

Section: Mir-486 Is Enriched In Myogenic Tissues But Reduced In Dystrmentioning

confidence: 99%

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

Alexander¹,

Casar²,

Matsuki³

et al. 2014

J. Clin. Invest.

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124

122

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Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which resultsin dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmd mdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmd mdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle-specific miR-486 overexpression in Dmd mdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle.

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Serum Transaminase Levels in Boys With Duchenne and Becker Muscular Dystrophy

Abstract: By recognizing muscle as a potential source of serum transaminase levels, clinicians can avoid unnecessary and invasive procedures, expedite clinical diagnosis, and avoid unnecessary cessation of concomitant drug therapy.

Cited by 76 publications

References 13 publications

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

Candidate biomarkers for the diagnosis and prognosis of drug‐induced liver injury: An international collaborative effort

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

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