Oxidative Stress, Redox Signaling Pathways, and Autophagy in Cachectic Muscles of Male Patients with Advanced COPD and Lung Cancer
Abstract
Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were i…
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MDA-protein adducts are increased both at the muscular and systemic levels in COPD patients.
“MDA-protein adducts are also increased both at the muscular and systemic levels in COPD patients [123].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [123]
A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation in COPD quadriceps.
“A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation (another marker of activation) in COPD quadriceps [123,182,183].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [123]
Two studies reported increased ultrastructural autophagosome counts in the quadriceps and/or tibialis anterior of COPD patients.
“Furthermore, two studies reported increased ultrastructural autophagosome counts, respectively, in the quadriceps [123] and both in the quadriceps and tibialis anterior [182].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [123]
Puig-Vilanova and colleagues reported an increase in p38-MAPK levels in COPD quadriceps but an unchanged ERK1/2 expression.
“Puig-Vilanova and colleagues reported an increase in p38-MAPK levels in COPD quadriceps but an unchanged ERK1/2 expression [123].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [123]
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Protein breakdown in cancer cachexia
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Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting
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“A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation (another marker of activation) in COPD quadriceps [123,182,183].”
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- Authors
- Puig-Vilanova, E., Rodriguez, D. A., Lloreta, J., Ausin, P., Pascual-Guardia, S., Broquetas, J., Roca, J., Gea, J., & Barreiro, E.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Parc de Salut (ES)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Barreiro, Esther
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 79
- Pages
- 91-108
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2057140087
- Cited by
- 167
- References
- 6
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 6 · 2023: 5 · 2022: 17 · 2021: 19 · 2020: 18 · 2019: 17 · 2018: 17 · 2017: 18 · 2016: 19 · 2015: 11 · 2014: 1
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- muscle atrophy, chronic obstructive pulmonary disease, lung cancer, oxidative stress, redox signaling, autophagy, ubiquitination, NF-κB, FOXO, inflammation, muscle protein degradation, mitochondrial function, vastus lateralis
- MeSH terms
- Aged, Autophagy, Cachexia, Humans, Lung Neoplasms, Male, Middle Aged, Oxidation-Reduction, Case-Control Studies, Oxidative Stress, Muscle, Skeletal, Pulmonary Disease, Chronic Obstructive
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