Sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin‐deficient mdx mice

  title={Sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin‐deficient mdx mice},
  author={Renato Ferretti and Maria Julia Marques and Adriana Pertille and Humberto Santo Neto},
  journal={Muscle \& Nerve},
In the mdx mouse model of Duchenne muscular dystrophy, the lack of dystrophin is associated with increased calcium levels and skeletal muscle myonecrosis. The intrinsic laryngeal muscles (ILM) are protected and do not undergo myonecrosis. We investigated whether this protection is related to an increased expression of calcium‐binding proteins, which may protect against the elevated calcium levels seen in dystrophic fibers. The expression of sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and… 

Increased sarcolipin expression and decreased sarco(endo)plasmic reticulum Ca2+ uptake in skeletal muscles of mouse models of Duchenne muscular dystrophy

The data suggest that sarcolipin upregulation is a common secondary alteration in all dystrophic muscles and contributes to the abnormal elevation of intracellular Ca2+ concentration via SERCA inhibition.

Calcium‐binding proteins in skeletal muscles of the mdx mice: potential role in the pathogenesis of Duchenne muscular dystrophy

Differential levels of the calcium‐handling proteins may be involved in the pathogenesis of myonecrosis in mdx muscles, and understanding the signaling mechanisms involving Ca2+‐calmodulin activation and calsequestrin expression may be a valuable way to develop new therapeutic approaches to the dystrophinopaties.

Stretch-activated calcium channel protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice.

It is suggested that different levels of the stretch-activated calcium channel protein TRPC1 may contribute to the different degrees of the dystrophic phenotype seen in mdx mice.

Postdevelopmental knockout of Orai1 improves muscle pathology in a mouse model of Duchenne muscular dystrophy.

Postdevelopmental, muscle-specific ablation of Orai1 in mdx mice abolishes excessive constitutive and store-operated Ca2+ entry, improves muscular dystrophy pathology, and promotes sarcolemmal

Changes in calsequestrin, TNF‐α, TGF‐β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles

A positive correlation between histopathology and cytokine levels was observed only in the diaphragm, suggesting that TNF‐α and TGF‐β serve as markers of dystrophy primarily for the diphragm.

Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle.

It is shown that the dystrophic phenotype observed in δ-sarcoglycan–null mice and dystrophin mutant mdx mice is dramatically improved by skeletal muscle–specific overexpression of sarcoplasmic reticulum Ca(2+) ATPase 1 (SERCA1).

Dysregulation of calcium homeostasis in muscular dystrophies

Recent advances in the understanding of calcium ion cycling through the sarcolemma, the sarcoplasmic reticulum and mitochondria, and its involvement in the pathogenesis of muscular dystrophies are summarized.

Cardiac and Respiratory Dysfunction in Duchenne Muscular Dystrophy and the Role of Second Messengers

Understanding the mechanisms behind the fine regulation of Ca2+‐NO may be important for a noninterventional and noninvasive supportive approach to treat D MD patients, improving the quality of life and natural history of DMD patients.

Overexpression of SERCA1a in the mdx diaphragm reduces susceptibility to contraction-induced damage.

Although the precise pathophysiological mechanism of muscle damage in dystrophin-deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne

Isobaric Tagging-Based Quantification for Proteomic Analysis: A Comparative Study of Spared and Affected Muscles from mdx Mice at the Early Phase of Dystrophy

Overall, the shotgun technique proved to be suitable to perform quantitative comparisons between distinct dystrophic muscles and allowed the suggestion of new potential biomarkers and drug targets for dystrophinopaties.



Drastic reduction of sarcalumenin in Dp427 (dystrophin of 427 kDa)-deficient fibres indicates that abnormal calcium handling plays a key role in muscular dystrophy.

It is shown that a key luminal Ca2+-binding protein SAR (sarcalumenin) is affected in mdx skeletal-muscle fibres, and this confirms the idea that abnormalCa2+ cycling is involved in Ca2-induced myonecrosis.

Subproteomics analysis of Ca+-binding proteins demonstrates decreased calsequestrin expression in dystrophic mouse skeletal muscle.

The reduced 2D 'Stains-All' pattern of luminal Ca(2+)-binding proteins in mdx preparations supports the calcium hypothesis of muscular dystrophy.

Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle.

Although the reduction in dystrophin-associated glycoproteins is the primary pathophysiological consequence of the deficiency in dystrophin, little is known about the secondary abnormalities leading

Comparative analysis of Dp427-deficient mdx tissues shows that the milder dystrophic phenotype of extraocular and toe muscle fibres is associated with a persistent expression of beta-dystroglycan.

This study suggests that the rescue of dystrophin-associated glycoproteins, and possibly the increased removal of cytosolic Ca2+ ions, might also play an important role in protecting muscle cells from necrotic changes.

Targeted Disruption of the ATP2A1 Gene Encoding the Sarco(endo)plasmic Reticulum Ca2+ ATPase Isoform 1 (SERCA1) Impairs Diaphragm Function and Is Lethal in Neonatal Mice*

The absence ofSERCA1 in type II fibers, and the absence of compensatory increases in other Ca2+ handling proteins, coupled with the marked increase in contractile function required of the diaphragm muscle to support postnatal respiration, can account for respiratory failure in term SERCA1-null mice.

Increased calcium influx in dystrophic muscle

The results suggest that increased calcium influx, as a result of increased leak channel activity, could result in the elevated [Ca2+]i in dystrophic muscle.

Dystrophin protects the sarcolemma from stresses developed during muscle contraction.

It is demonstrated that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture, which strongly support the proposition that the primary function of dyStrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction.

Impaired Ca2+ Store Functions in Skeletal and Cardiac Muscle Cells from Sarcalumenin-deficient Mice*

It is demonstrated that SAR plays important roles in improving the Ca2+ handling functions of the SR in striated muscle.