Sarco(endo)plasmic reticulum Ca2+-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx mice

Cleverdon, Riley; Braun, Jessica; Geromella, Mia S.; Whitley, Kennedy; Markó, Daniel; Hamstra, Sophie I.; Roy, Brian D.; MacPherson, Rebecca E. K.; Fajardo, Val A.

doi:10.1016/j.isci.2022.104972

Cited by 10 publications

(12 citation statements)

References 49 publications

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“…Interestingly, in the case of the mdx:utr −/− mouse and DBA/2J mdx, SERCA activity is much more suppressed than in the case of the classical C57 mdx mouse [109,121,122], and this, apparently, contributes to a more pronounced calcium overload and, as a result, development of dystrophy. At the same time, gastrocnemius DBA/2J mdx mice show an increase in the expression of SERCA1 and SERCA2, which, as in other cases of increased activity of SERCA isoforms, may indicate an adaptive response aimed at improving SR Ca 2+ handling, but this, apparently, is not enough [122]. Along with this, transgenic overexpression of SERCA1 in skeletal muscles of mdx and mdx:utr −/− mice improved the pathology [123,124].…”

Section: Sr Channel Abnormalities In Dmdmentioning

confidence: 96%

Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

Dubinin

Belosludtsev

2023

IJMS

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Duchenne muscular dystrophy (DMD) is caused by the absence of the dystrophin protein and a properly functioning dystrophin-associated protein complex (DAPC) in muscle cells. DAPC components act as molecular scaffolds coordinating the assembly of various signaling molecules including ion channels. DMD shows a significant change in the functioning of the ion channels of the sarcolemma and intracellular organelles and, above all, the sarcoplasmic reticulum and mitochondria regulating ion homeostasis, which is necessary for the correct excitation and relaxation of muscles. This review is devoted to the analysis of current data on changes in the structure, functioning, and regulation of the activity of ion channels in striated muscles in DMD and their contribution to the disruption of muscle function and the development of pathology. We note the prospects of therapy based on targeting the channels of the sarcolemma and organelles for the correction and alleviation of pathology, and the problems that arise in the interpretation of data obtained on model dystrophin-deficient objects.

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Section: Sr Channel Abnormalities In Dmdmentioning

confidence: 96%

Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

Dubinin

Belosludtsev

2023

IJMS

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“…However, the addition of oxalate may not be truly be physiologically representative and thus, it is important to consider the desired outcome measure. In conditions where severe Ca 2+ dyshomeostasis is expected, (e.g., diseased or damaged states 4 ) it is suggested that oxalate be added to allow for a read of Ca 2+ uptake. For more information, see troubleshooting 1 .…”

Section: Before You Beginmentioning

confidence: 99%

“…In cases where the starting Ca 2+ levels appear high, or are high in a specific experimental group (e.g., Cleverdon et al. 4 ), a few things can be done. First, it is possible to add small amounts of 50 mM EGTA (0.2–0.5 μL) to the individual wells in order to bring all wells to a similar starting point prior to adding ATP and initiating uptake.…”

Section: Troubleshootingmentioning

confidence: 99%

Measuring SERCA-mediated calcium uptake in mouse muscle homogenates

Geromella¹,

Braun²,

Fajardo³

2023

STAR Protocols

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“…Mislocation and dysfunction of the sarcoplasmic reticulum (SR) and its Ca 2+ -regulating proteins also contribute to the loss of Ca 2+ homeostasis and play an important role in the progression of the disease in dystrophin-lacking muscles [155][156][157][158]. Surprisingly, although SR function has been studied with multiple other techniques [155,[158][159][160], histological tests to study the SR are not routinely performed in dystrophin-deficient muscles.…”

Section: Sarcoplasmic Reticulummentioning

confidence: 99%

Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy

Dubuisson

Versele

Planchon

et al. 2022

IJMS

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Duchenne muscular dystrophy (DMD) is a progressive disease caused by the loss of function of the protein dystrophin. This protein contributes to the stabilisation of striated cells during contraction, as it anchors the cytoskeleton with components of the extracellular matrix through the dystrophin-associated protein complex (DAPC). Moreover, absence of the functional protein affects the expression and function of proteins within the DAPC, leading to molecular events responsible for myofibre damage, muscle weakening, disability and, eventually, premature death. Presently, there is no cure for DMD, but different treatments help manage some of the symptoms. Advances in genetic and exon-skipping therapies are the most promising intervention, the safety and efficiency of which are tested in animal models. In addition to in vivo functional tests, ex vivo molecular evaluation aids assess to what extent the therapy has contributed to the regenerative process. In this regard, the later advances in microscopy and image acquisition systems and the current expansion of antibodies for immunohistological evaluation together with the development of different spectrum fluorescent dyes have made histology a crucial tool. Nevertheless, the complexity of the molecular events that take place in dystrophic muscles, together with the rise of a multitude of markers for each of the phases of the process, makes the histological assessment a challenging task. Therefore, here, we summarise and explain the rationale behind different histological techniques used in the literature to assess degeneration and regeneration in the field of dystrophinopathies, focusing especially on those related to DMD.

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Sarco(endo)plasmic reticulum Ca2+-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx mice

Cited by 10 publications

References 49 publications

Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

Measuring SERCA-mediated calcium uptake in mouse muscle homogenates

Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy

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