<scp>ER</scp> stress in skeletal muscle remodeling and myopathies

Afroze, Dil; Kumar, Ashok

doi:10.1111/febs.14358

Cited by 110 publications

(162 citation statements)

References 172 publications

(261 reference statements)

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…ERp44 is a pH‐regulated chaperone of the secretory pathway, which controls oxidative‐related protein misfolding in the ER . These results are in accordance with studies showing that ER stress is activated in several catabolic situations (denervation, starvation, high‐fat diet, cancer cachexia, and ageing) . The ER stress response can be activated by several stress factors (nutrient deprivation, reactive oxygen species, etc.)…”

Section: Discussionsupporting

confidence: 85%

Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Aniort

Stella

Philipponnet

et al. 2019

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome, and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients. Methods Muscle biopsies were performed during scheduled interventions in early‐stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients ( n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real‐time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered. Results We found an increased expression of several UPS and autophagy‐related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy‐related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxification, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co‐expression network analysis. Conclusions We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early‐stage LC vs. long‐term renal failure). This strongly suggests that a common atrophying programme e...

show abstract

Section: Discussionsupporting

confidence: 85%

Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Aniort

Stella

Philipponnet

et al. 2019

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…Because of the critical role played by the ER in many aspects of cellular function, it is perhaps unsurprising that dysfunction of the UPR proved to be a factor in the pathogenesis of many human diseases . Almost no tissues are spared from ER stress‐related damage and in this Special Issue of The FEBS Journal , the roles of ER stress in diseases affecting the lung, liver, skin, muscle and nervous system are each examined in detail .…”

mentioning

confidence: 97%

“…Dil Afroze and Ashok Kumar review the recent literature implicating ER stress in the biology of muscle . A tissue often overlooked in the study of ER stress, skeletal muscle has a highly specialized ER (the sarcoplasmic reticulum) that is central to excitation contraction coupling.…”

mentioning

confidence: 99%

Endoplasmic reticulum stress: a key player in human disease

Marciniak

2019

The FEBS Journal

View full text Add to dashboard Cite

This Special Issue comprises eleven excellent reviews that illustrate the role of ER stress in different human diseases, including myopathies and lung diseases, as well as in modulating liver dysfunction and inflammatory responses. These reviews also highlight the function of the UPR in neurodegenerative disorders and cancer, while discussing the potential benefits of targeting the UPR as a therapeutic approach. We hope you find these reviews interesting and informative and we thank the authors for these excellent contributions.

show abstract

“…Accumulating evidence suggests that the abundance and activity of various components of the UPR are increased in skeletal muscle of rodents and humans in multiple conditions of muscle growth and atrophy (5,10). For example, the expression of various ER stress and UPR markers is increased in skeletal muscle in response to both endurance and acute exercise (5,11). It has been reported that the cleaved form of ATF6a interacts with peroxisome proliferator-activated receptor-g coactivator-1a to induce an adaptive UPR in skeletal muscle after acute exercise (12).…”

mentioning

confidence: 99%

“…It has been reported that the cleaved form of ATF6a interacts with peroxisome proliferator-activated receptor-g coactivator-1a to induce an adaptive UPR in skeletal muscle after acute exercise (12). Moreover, markers of ER stress and the UPR have been found to be elevated in skeletal muscle undergoing atrophy (11,13,14). For example, levels of CCAAT/ enhancer-binding protein (C/EBP) homologous protein (CHOP), a downstream target of the PERK arm of the UPR, are increased in skeletal muscle of mice upon denervation.…”

mentioning

confidence: 99%

PERK regulates skeletal muscle mass and contractile function in adult mice

Gallot

Bohnert²,

Straughn³

et al. 2018

FASEB j.

Self Cite

View full text Add to dashboard Cite

Skeletal muscle mass is regulated by the coordinated activation of several anabolic and catabolic pathways. The endoplasmic reticulum (ER) is a major site of protein folding and a reservoir for calcium ions. Accretion of misfolded proteins or depletion in calcium concentration causes stress in the ER, which leads to the activation of a signaling network known as the unfolded protein response (UPR). In the present study, we investigated the role of the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR in the regulation of skeletal muscle mass and function in naive conditions and in a mouse model of cancer cachexia. Our results demonstrate that the targeted inducible deletion of PERK reduces skeletal muscle mass, strength, and force production during isometric contractions. Deletion of PERK also causes a slow-to-fast fiber type transition in skeletal muscle. Furthermore, short hairpin RNA-mediated knockdown or pharmacologic inhibition of PERK leads to atrophy in cultured myotubes. While increasing the rate of protein synthesis, the targeted deletion of PERK leads to the increased expression of components of the ubiquitin-proteasome system and autophagy in skeletal muscle. Ablation of PERK also increases the activation of calpains and deregulates the gene expression of the members of the FGF19 subfamily. Furthermore, the targeted deletion of PERK increases muscle wasting in Lewis lung carcinoma tumor-bearing mice. Our findings suggest that the PERK arm of the UPR is essential for the maintenance of skeletal muscle mass and function in adult mice.-Gallot, Y. S., Bohnert, K. R., Straughn, A. R., Xiong, G., Hindi, S. M., Kumar, A. PERK regulates skeletal muscle mass and contractile function in adult mice.

show abstract

ER stress in skeletal muscle remodeling and myopathies

Cited by 110 publications

References 172 publications

Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Endoplasmic reticulum stress: a key player in human disease

PERK regulates skeletal muscle mass and contractile function in adult mice

Contact Info

Product

Resources

About