Endoplasmic reticulum stress promotes sepsis‐induced muscle atrophy via activation of STAT3 and Smad3

Zheng, Yangfan; Dai, Hongkai; Chen, Renyu; Zhong, Yanyan; Zhou, Chenchen; Wang, Yurou; Chen, Zhan; Luo, Jin

doi:10.1002/jcp.30950

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…The ER stress is a potential factor for muscle mass wasting (Zheng et al., 2023 ). PERK and ATF6 are activated as sensing proteins of ER stress (Hetz, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is suggested that AGEs may disrupt proteostasis and thereby induce skeletal muscle dysfunctions or have a biphasic effect, thereby inhibiting protein degradation for short periods and enhancing it for longer periods. The ER stress is a potential factor for muscle mass wasting (Zheng et al, 2023). PERK and ATF6 are activated as sensing proteins of ER stress (Hetz, 2012).…”

Section: Muthyalaiahmentioning

confidence: 99%

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Direct and acute effects of advanced glycation end products on proteostasis in isolated mouse skeletal muscle

Zhao,

Iyama,

Kurogi

et al. 2024

Physiological Reports

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Advanced glycation end products (AGEs) have been implicated in several skeletal muscle dysfunctions. However, whether the adverse effects of AGEs on skeletal muscle are because of their direct action on the skeletal muscle tissue is unclear. Therefore, this study aimed to investigate the direct and acute effects of AGEs on skeletal muscle using an isolated mouse skeletal muscle to eliminate several confounders derived from other organs. The results showed that the incubation of isolated mouse skeletal muscle with AGEs (1 mg/mL) for 2–6 h suppressed protein synthesis and the mechanistic target of rapamycin signaling pathway. Furthermore, AGEs showed potential inhibitory effects on protein degradation pathways, including autophagy and the ubiquitin–proteasome system. Additionally, AGEs stimulated endoplasmic reticulum (ER) stress by modulating the activating transcription factor 6, PKR‐like ER kinase, C/EBP homologous protein, and altered inflammatory cytokine expression. AGEs also stimulated receptor for AGEs (RAGE)‐associated signaling molecules, including mitogen‐activated protein kinases. These findings suggest that AGEs have direct and acute effect on skeletal muscle and disturb proteostasis by modulating intracellular pathways such as RAGE signaling, protein synthesis, proteolysis, ER stress, and inflammatory cytokines.

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“…The ER stress is a potential factor for muscle mass wasting (Zheng et al., 2023 ). PERK and ATF6 are activated as sensing proteins of ER stress (Hetz, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Muthyalaiahmentioning

confidence: 99%

Direct and acute effects of advanced glycation end products on proteostasis in isolated mouse skeletal muscle

Zhao,

Iyama,

Kurogi

et al. 2024

Physiological Reports

View full text Add to dashboard Cite

show abstract

“…In a former research study [16], ER stress is activated and involved in disuse-induced muscle atrophy. Additionally, our previous study [17] reported that ER stress promotes sepsis-induced muscle atrophy. The upregulation of biomarkers of ER stress follows an analogous trend to that of atrophy-related genes, which reveals a correlation between ER stress and sepsis-induced muscle atrophy.…”

Section: Introductionmentioning

confidence: 93%

N-Acetylcysteine Attenuates Sepsis-Induced Muscle Atrophy by Downregulating Endoplasmic Reticulum Stress

Chen,

Zheng,

Zhou

et al. 2024

Biomedicines

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(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused by several diseases, whereas its effect on sepsis-induced muscle atrophy has not been reported. The present study investigated the effect of NAC on sepsis-induced muscle atrophy and its possible mechanisms. (2) Methods: The effect of NAC on sepsis-induced muscle atrophy was assessed in vivo and in vitro using cecal ligation and puncture-operated (CLP) C57BL/6 mice and LPS-treated C2C12 myotubes. We used immunofluorescence staining to analyze changes in the cross-sectional area (CSA) of myofibers in mice and the myotube diameter of C2C12. Protein expressions were analyzed by Western blotting. (3) Results: In the septic mice, the atrophic response manifested as a reduction in skeletal muscle weight and myofiber cross-sectional area, which is mediated by muscle-specific ubiquitin ligases—muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle ring finger 1 (MuRF1). NAC alleviated sepsis-induced skeletal muscle wasting and LPS-induced C2C12 myotube atrophy. Meanwhile, NAC inhibited the sepsis-induced activation of the endoplasmic reticulum (ER) stress signaling pathway. Furthermore, using 4-Phenylbutyric acid (4-PBA) to inhibit ER stress in LPS-treated C2C12 myotubes could partly abrogate the anti-muscle-atrophy effect of NAC. Finally, NAC alleviated myotube atrophy induced by the ER stress agonist Thapsigargin (Thap). (4) Conclusions: NAC can attenuate sepsis-induced muscle atrophy, which may be related to downregulating ER stress.

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“…ER stress can also cause impaired muscle protein synthesis, leading to muscle atrophy. There is a strong link between ER stress and muscle atrophy and dysfunction 12,26 . Therefore, reducing ER stress is an effective strategy to improve VIDD.…”

Section: Introductionmentioning

confidence: 99%

“…There is a strong link between ER stress and muscle atrophy and dysfunction. 12 , 26 Therefore, reducing ER stress is an effective strategy to improve VIDD.…”

Section: Introductionmentioning

confidence: 99%

Irisin attenuates ventilator‐induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK

Zhang,

Tu,

Guan

et al. 2024

J Cellular Molecular Medi

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Mechanical ventilation (MV) is an essential life‐saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator‐induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague–Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross‐sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

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Endoplasmic reticulum stress promotes sepsis‐induced muscle atrophy via activation of STAT3 and Smad3

Cited by 8 publications

References 52 publications

Direct and acute effects of advanced glycation end products on proteostasis in isolated mouse skeletal muscle

Direct and acute effects of advanced glycation end products on proteostasis in isolated mouse skeletal muscle

N-Acetylcysteine Attenuates Sepsis-Induced Muscle Atrophy by Downregulating Endoplasmic Reticulum Stress

Irisin attenuates ventilator‐induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK

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