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

Abstract

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 Ca(2+)-ATPase and calsequestrin was examined in ILM and in nonspared limb muscles of control and mdx mice using immunofluorescence and immunoblotting. Dystrophic ILM presented a significant increase in the proteins studied when compared to controls. The increase of Ca(2+)-handling proteins in dystrophic ILM may permit better maintenance of calcium homeostasis, with the consequent absence of myonecrosis. The results further support the concept that abnormal Ca(2+)-handling is involved in dystrophinopathies. Muscle Nerve, 2009.

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

“…This finding is in agreement with previous observations in the mdx EOM using Western blotting analysis [31]. Other mdx spared muscles, such as the intrinsic laryngeals, also show higher levels of SERCA1 in comparison to normal ILM muscles [40]. Moreover, we observed that the calcium buffering proteins sarcalumenin and calsequestrin 1 [41], [42] were increased in EOM compared to DIA, even in the control group.…”

Proteomic profiling of naturally protected extraocular muscles from the dystrophin-deficient mdx mouse

“…Low levels of CSQ seem to exacerbate abnormal cytosolic Ca 2+ -handling by impairing luminal Ca 2+ -buffering in the dystrophic sarcoplasmic reticulum. These pathological alterations appear not to be present in mdx EOM tissue [31], which agrees with the previously reported resistance of dystrophic EOM fibers to Ca 2+ -induced muscle degeneration [15]. The drastic increase in molecular chaperones suggests that mdx EOM is capable of sustained cellular stress responses, involving both low-and high-molecular-mass Hsp elements.…”

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

“…It is also very interesting to note that muscles spared of disease in mdx mice, the laryngeal muscles, show significant overexpression of SERCA1 with disease (40). More recently, in direct support of our study, AAV-SERCA1a gene transfer in mdx mice was shown to decrease centrally located nuclei in the diaphragm and to reduce eccentric contraction-induced damage (41).…”