Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts

Rohman, Mohammad Saifur; Emoto, Noriaki; Takeshima, Yasuhiro; Yokoyama, Mitsuhiro; Matsuo, Masafumi

doi:10.1016/j.bbrc.2003.09.005

Cited by 32 publications

(24 citation statements)

References 37 publications

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“…This could lead to raised cytosolic Ca 2+ levels and the activation of Ca 2+ -dependent proteases causing fibre destruction. In this respect, our immunoblotting result showing a decreased expression of the cardiac RyR2 isoform of the ryanodine receptor Ca 2+ release channel and the slow/cardiac SERCA2 isoform of the sarcoplasmic reticulum Ca 2+ -ATPase agrees with a recent report by Rohman et al [43] that demonstrated a decreased gene expression of both Ca 2+ regulatory elements. This suggests that abnormal Ca 2+ handling in the dystrophic heart possibly leads to impaired excitation-contraction coupling and cardiac relaxation cycles.…”

Section: Molecular Pathogenesis Of Muscular Dystrophy-associated Cardsupporting

confidence: 93%

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Lohan

Culligan

Ohlendieck

2005

BioMed Research International

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Although Duchenne muscular dystrophy is primarily categorised as a skeletal muscle disease, deficiency in the membrane cytoskeletal protein dystrophin also affects the heart. The central transsarcolemmal linker between the actin membrane cytoskeleton and the extracellular matrix is represented by the dystrophin-associated dystroglycans. Chemical cross-linking analysis revealed no significant differences in the dimeric status of the α-/β-dystroglycan subcomplex in the dystrophic mdx heart as compared to normal cardiac tissue. In analogy to skeletal muscle fibres, heart muscle also exhibited a greatly reduced abundance of both dystroglycans in dystrophin-deficient cells. Immunoblotting demonstrated that the degree of reduction in α-dystroglycan is more pronounced in matured mdx skeletal muscle as contrasted to the mdx heart. The fact that the deficiency in dystrophin triggers a similar pathobiochemical response in both types of muscle suggests that the cardiomyopathic complications observed in x-linked muscular dystrophy might be initiated by the loss of the dystrophin-associated surface glycoprotein complex.

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Section: Molecular Pathogenesis Of Muscular Dystrophy-associated Cardsupporting

confidence: 93%

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Lohan

Culligan

Ohlendieck

2005

BioMed Research International

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“…Heart failure accounts for 30% of the mortality in DMD patients 170 . An MDX mouse, which is a model of DMD and lacks the protein dystrophin, has decreased levels of SR luminal Ca 2+ -binding proteins 171 , decreased SERCA2a expression 172 , and an increase in resting [Ca 2+ ] i 173 . Patients with DMD are at increased risk for fatal cardiac arrhythmias 170, 174 .…”

Section: Defective Ecc and Alterations Of Ca2+ Handling Proteins mentioning

confidence: 99%

Mechanisms of Altered Ca ²⁺ Handling in Heart Failure

Luo

Anderson

2013

Circulation Research

313

250

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Ca2+ plays a crucial role in connecting membrane excitability with contraction in myocardium. The hallmark features of heart failure are mechanical dysfunction and arrhythmias; defective intracellular Ca2+ homeostasis is a central cause of contractile dysfunction and arrhythmias in failing myocardium. Defective Ca2+ homeostasis in heart failure can result from pathological alteration in the expression and activity of an increasingly understood collection of Ca2+ homeostatic binding proteins, ion channels and enzymes. This review focuses on the molecular mechanisms of defective Ca2+ cycling in heart failure and consider how fundamental understanding of these pathways may translate into novel and innovative therapies.

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“…Abnormalities in calcium handling could also be a mechanism that contributes to the observed increase in heart rate in flies, hypercontractility in worms and hypercontraction and death of mouse mdx myocardial cells (see Yasuda et al, 2005). Furthermore, mdx hearts have been shown to have defects in Ca 2+ handling proteins, including decreased cardiac sarcoplasmic reticulum Ca 2+ ATPase 2 (SERCA2) mRNA and delayed normalization of intracellular Ca 2+ concentration (Rohman et al, 2003;Williams & Allen, 2007). Drosophila has been proven to be a valuable model to dissect the DMD pathogenicity (Shcherbata et al, 2007), including that of the heart (this study).…”

Section: Drosophila As a Model For Dilated Cardiomyopathymentioning

confidence: 99%

Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype

et al. 2008

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SummaryA number of studies have been conducted recently on the model organism Drosophila to determine the function of genes involved in human disease, including those implicated in neurological disorders, cancer and metabolic and cardiovascular diseases. The simple structure and physiology of the Drosophila heart tube together with the available genetics provide a suitable in vivo assay system for studying cardiac gene functions. In our study, we focus on analysis of the role of dystrophin (Dys) in heart physiology. As in humans, the Drosophila dys gene encodes multiple isoforms, of which the large isoforms ( DLPs ) and a truncated form ( Dp117 ) are expressed in the adult heart. Here, we show that the loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi-mediated knockdown in the mesoderm also shortens lifespan. Knockdown of all or deletion of the large isoforms increases the heart rate by shortening the diastolic intervals (relaxation phase) of the cardiac cycle. Morphologically, loss of the large DLPs isoforms causes a widening of the cardiac tube and a lower fractional shortening, a phenotype reminiscent of dilated cardiomyopathy. The dilated dys mutant phenotype was reversed by expressing a truncated mammalian form of dys ( Dp116 ). Our results illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and other muscular-dystrophy-associated phenotypes.

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Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts

Cited by 32 publications

References 37 publications

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Mechanisms of Altered Ca ²⁺ Handling in Heart Failure

Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype

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Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts

Cited by 32 publications

References 37 publications

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Deficiency in Cardiac Dystrophin Affects the Abundance of the α‐/β‐Dystroglycan Complex

Mechanisms of Altered Ca 2+ Handling in Heart Failure

Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype

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Mechanisms of Altered Ca ²⁺ Handling in Heart Failure