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

Publisher: Springer Country of Publication: Germany NLM ID: 9506663 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-119X (Electronic) Linking ISSN: 09486143 NLM ISO Abbreviation: Histochem Cell Biol Subsets: MEDLINE

Original Publication: Berlin : Springer,

Lung Diseases*/metabolism ; Sarcopenia*/metabolism; Calcium/metabolism ; Humans ; Oxidative Stress ; Sarcoplasmic Reticulum/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism

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 Ca ²⁺ 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.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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1901090157 University of Sharjah; 1901090168 University of Sharjah

Keywords: COPD; Oxidative stress; SERCA ATPase; SR stress; Sarcopenia

EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SY7Q814VUP (Calcium)

Date Created: 20211019 Date Completed: 20220316 Latest Revision: 20220316

20221213

10.1007/s00418-021-02043-3

34665327