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

Summary

The DBA/2J (D2) mdx mouse is a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca ²⁺-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. Both D2 and C57 mdx mice exhibited signs of impaired Ca ²⁺ uptake in the gastrocnemius, diaphragm, and left ventricle; however, the level of impairment was more severe in D2 mdx mice. Reductions in maximal SERCA activity were also more prominent in the D2 mdx gastrocnemius and diaphragm when compared to those from C57 mdx mice; however, there were no differences detected in the left ventricle. Across all muscles, D2 mdx mice had the highest levels of oxidative stress as indicated by protein nitrosylation and/or nitration. In conclusion, our study shows that SERCA function is more impaired in young D2 mdx mice compared with age-matched C57 mdx mice.

Graphical abstract

Highlights

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  Ca ²⁺ uptake is severely impaired in muscles from young DBA/2J (D2) mdx mice

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  Maximal SERCA activity is lowered to a greater degree in muscles from D2 mdx mice

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  Muscles from young D2 mdx mice have higher levels of oxidative/nitrosative stress

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  Worsened SERCA function may contribute to worsened muscle pathology in D2 mdx mice

Abstract

Pathophysiology; Cell biology