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Sarcopenia in pulmonary diseases is associated with elevated sarcoplasmic reticulum stress and myonuclear disorganization

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Abstract

Chronic obstructive pulmonary disease (COPD) is frequently associated with age-related muscle loss or sarcopenia. However, the exact molecular mechanism of muscle loss in COPD remains elusive. We investigated the association of chronic dysregulation of sarcoplasmic reticulum (SR) protein homeostasis (a condition called SR stress) and myonuclear disorganization with sarcopenia in patients with COPD. Markers of SR stress and their downstream consequences, including apoptosis and inflammation, were upregulated in patients with COPD. The maximal SR Ca2+ ATPase (SERCA) activity was significantly reduced in advanced COPD as compared to healthy controls. Single muscle fiber diameter and cytoplasmic domain per myonucleus were significantly smaller in patients with advanced COPD than in healthy controls. Increased disruption of myonuclear organization was found in the COPD patients as compared to healthy controls. These changes in SR dysfunction were accompanied by elevated global levels of oxidative stress, including lipid peroxidation and mitochondrial reactive oxygen species (ROS) production. Altogether, our data suggest that muscle weakness in advanced COPD is in part associated with the disruption of SR protein and calcium homeostasis and their pathological consequences.

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Funding

This work was supported by Target (1901090168) and competitive grants (1901090157) from the University of Sharjah to Rizwan Qaisar.

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Authors and Affiliations

  1. Basic Medical Sciences, College of Medicine, University of Sharjah, 27272, Sharjah, United Arab Emirates

    Rizwan Qaisar

  2. Department of Biochemistry, Gomal Medical College, Dera Ismail Khan, 29050, Pakistan

    Shahjahan Ustrana & Tahir Muhammad

  3. Al-Qassimi Hospital, 27272, Sharjah, United Arab Emirates

    Islam Shah

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  1. Rizwan Qaisar
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  2. Shahjahan Ustrana
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  4. Islam Shah
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Conceptualization by RQ, patients’ recruitment and data collection by MQ and TM, data analysis by RQ, funding acquisition by RQ, and preparation of the manuscript by RQ. All authors read and approved the manuscript.

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Correspondence to Rizwan Qaisar.

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All experimental protocols were approved by the hospital research ethics committees of GMC (REC-19-04-1801, dated: 04/03/2019). The study was conducted under the tenets of the Declaration of Helsinki (World Medical Association 2013).

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Qaisar, R., Ustrana, S., Muhammad, T. et al. Sarcopenia in pulmonary diseases is associated with elevated sarcoplasmic reticulum stress and myonuclear disorganization. Histochem Cell Biol 157, 93–105 (2022). https://doi.org/10.1007/s00418-021-02043-3

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