Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases

Barreiro, Esther; Salazar‐Degracia, Anna; Sancho-Muñoz, Antonio; Gea, Joaquim

doi:10.1002/jcp.27789

Cited by 27 publications

(43 citation statements)

References 61 publications

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“…ER stress and disruptions in the UPR, calcium homeostasis, and proteostasis have been reported in clinical and experimental cachexia and other inflammation-driven muscle diseases such as myositis, suggesting a link between increased levels of inflammatory cytokines and ER stress in skeletal muscle [45]. Recent studies have further demonstrated that the markers of ER stress and the UPR are elevated in skeletal muscle in various catabolic conditions, including cancer [46][47][48]. TRAF6 is an E3 ubiquitin ligase and an adaptor protein that is involved in the downstream activation of multiple signaling pathways in response to cytokines and microbial products.…”

Section: Er Stress Upr and Cancer Cachexiamentioning

confidence: 99%

“…A recent study by Barreiro et al indicates elevated marker of all the three arms of the UPR in vastus lateralis muscle in lung cancer cachectic patients. However, a caveat of the study was that while non cachectic lung cancer patients should have been used as a control, the comparisons were made with healthy subjects [48]. Intriguingly, instead of providing protection, pharmacological inhibition of ER stress using 4-phenylbutyrate (4-PBA), a chemical chaperone that attenuates ER stress [52,53], was found to exacerbate the loss of muscle mass in LLC tumor-bearing mice.…”

Section: Er Stress Upr and Cancer Cachexiamentioning

confidence: 99%

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ER Stress and Unfolded Protein Response in Cancer Cachexia

Roy

Kumar

2019

Cancers

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Cancer cachexia is a devastating syndrome characterized by unintentional weight loss attributed to extensive skeletal muscle wasting. The pathogenesis of cachexia is multifactorial because of complex interactions of tumor and host factors. The irreversible wasting syndrome has been ascribed to systemic inflammation, insulin resistance, dysfunctional mitochondria, oxidative stress, and heightened activation of ubiquitin-proteasome system and macroautophagy. Accumulating evidence suggests that deviant regulation of an array of signaling pathways engenders cancer cachexia where the human body is sustained in an incessant self-consuming catabolic state. Recent studies have further suggested that several components of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) are activated in skeletal muscle of animal models and muscle biopsies of cachectic cancer patients. However, the exact role of ER stress and the individual arms of the UPR in the regulation of skeletal muscle mass in various catabolic states including cancer has just begun to be elucidated. This review provides a succinct overview of emerging roles of ER stress and the UPR in cancer-induced skeletal muscle wasting.

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Section: Er Stress Upr and Cancer Cachexiamentioning

confidence: 99%

Section: Er Stress Upr and Cancer Cachexiamentioning

confidence: 99%

ER Stress and Unfolded Protein Response in Cancer Cachexia

Roy

Kumar

2019

Cancers

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“…in addition, the mrna and protein expression levels of ATF6 were significantly upregulated in the vastus lateralis (Vl) of patients with lc-induced cachexia, and aTF6 was also discovered to potentially interact with protein degradation pathways, such as the uPS. The gene expression levels of MAFbx and MuRF1 were also significantly upregulated in the Vl of lc-induced cachexia patients compared with healthy controls (124). evidence from previous studies has also revealed that multiple markers of er stress and the uPr, such as PerK, ire1a and aTF6, were highly activated in the skeletal muscle of llc and apc(Min/+) mouse models of cancer cachexia.…”

Section: Er Stress and Mitochondrial Dysfunctionmentioning

confidence: 71%

“…Previous studies have reported emerging roles of er stress and the uPr in cancer cachexia-induced muscle atrophy (31,123,124). in fact, markers of er stress and the uPr were upregulated in the muscles of cachectic patients with cancer (124).…”

Section: Er Stress and Mitochondrial Dysfunctionmentioning

confidence: 91%

Molecular mechanisms of cancer cachexia‑induced muscle atrophy (Review)

Huang

et al. 2020

Mol Med Rep

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Muscle atrophy is a severe clinical problem involving the loss of muscle mass and strength that frequently accompanies the development of numerous types of cancer, including pancreatic, lung and gastric cancers. cancer cachexia is a multifactorial syndrome characterized by a continuous decline in skeletal muscle mass that cannot be reversed by conventional nutritional therapy. The pathophysiological characteristic of cancer cachexia is a negative protein and energy balance caused by a combination of factors, including reduced food intake and metabolic abnormalities. numerous necessary cellular processes are disrupted by the presence of abnormal metabolites, which mediate several intracellular signaling pathways and result in the net loss of cytoplasm and organelles in atrophic skeletal muscle during various states of cancer cachexia. currently, the clinical morbidity and mortality rates of patients with cancer cachexia are high. once a patient enters the cachexia phase, the consequences are difficult to reverse and the treatment methods for cancer cachexia are very limited. The present review aimed to summarize the recent discoveries regarding the pathogenesis of cancer cachexia-induced muscle atrophy and provided novel ideas for the comprehensive treatment to improve the prognosis of affected patients. Contents 1. introduction 2. activation of the uPS 3. Induction of proinflammatory factors 4. regulation of signaling pathways, transcription factors and micrornas (mirnas/mirs) 5. cell autophagy/lysosomal and ca 2+-dependent protein degradation pathways 6. endoplasmic reticulum stress and mitochondrial dysfunction 7. other receptors and substances that affect metabolism 8. Treatment of muscle atrophy caused by cancer cachexia 9. conclusion

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“…To further investigate the role of Rcn3 in pulmonary diseases, selective Rcn3 knockout in AECIIs were successfully established in our laboratory, and have been employed to study the function of Rcn3 in the development of lung fibrosis [9]. We hereby established the PPE-induced An accumulation of misfolded and unfolded proteins in ER lumen under physiological or pathological stress results in ER stress [29]. To restore protein homeostasis, the unfolded protein response (UPR) is mediated and activated by ER membrane protein sensors, which were regulated by GRP78 [30,31].…”

Section: Discussionmentioning

confidence: 99%

Suppression of Rcn3 in the alveolar epithelial cells may have beneficial effect against COPD

Zhang

Wang

Jin

et al. 2020

Preprint

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Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent lung disease worldwide and imposes increasing disease burdens globally. COPD is characterized by irreversible airflow obstruction. Emphysema is one of the primary pathological features causing the irreversible decline of pulmonary function, while the precise mechanisms behind emphysema remain unclear. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized in the secretory pathway of living cells. We have reported that Rcn3 in type II alveolar epithelial cell (AECIIs) plays a critical role in perinatal lung development and bleomycin-induced lung injury-repair. Since is associated with alveolar epithelial disruption, Rcn3 might be involved in the development of emphysema during COPD. Materials and Methods : We examined Rcn3 expression in lung specimens from patients (44 COPD patients and 26 non-COPD control patients) undergoing lung lobectomy or pneumonectomy. Mouse models of COPD and emphysema were established by cigarette smoke (CS) exposure and intratracheal installation of pancreatic porcine elastase (PPE), respectively. Rcn3 expression was detected in the lung tissues from these mice. Furthermore, conditional knockout (CKO) mice with Rcn3 deletion specific to AECIIs, were used to explore the role of Rcn3 in PPE-induced emphysema progression. Rcn3 protein expression in lung tissues were evaluated by Western blot and immunohistochemistry. Rcn3 mRNA expression in lung tissues was detected by qPCR.Results : Compared with non-COPD patients, Rcn3 expression was significantly increased in the lung specimens from COPD patients. Rcn3 expression was also significantly up-regulated in the lung tissues from COPD mice and emphysematous mice. Moreover, selective ablation of Rcn3 in AEC IIs significantly alleviated severity of the mouse emphysema in response to intratracheal installation of PPE.Conclusions: Our data, for the first time, indicated that Rcn3 in AECIIs might play a role in modulating the progression of emphysema, and thus be involved in the development of COPD. Suppression of Rcn3 expression in AECIIs may have a beneficial effect on COPD.This work was supported by National Natural Science Foundation of China (No. 81641004).

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Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases

Cited by 27 publications

References 61 publications

ER Stress and Unfolded Protein Response in Cancer Cachexia

ER Stress and Unfolded Protein Response in Cancer Cachexia

Molecular mechanisms of cancer cachexia‑induced muscle atrophy (Review)

Suppression of Rcn3 in the alveolar epithelial cells may have beneficial effect against COPD

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