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Apocynin prevents cigarette smoking‐induced loss of skeletal muscle mass and function in mice by preserving proteostatic signalling
- Source :
- British Journal of Pharmacology
- Publication Year :
- 2021
- Publisher :
- John Wiley and Sons Inc., 2021.
-
Abstract
- BACKGROUND AND PURPOSE Skeletal muscle dysfunction is a major comorbidity of chronic obstructive pulmonary disease (COPD). This type of muscle dysfunction may be a direct consequence of oxidative insults evoked by cigarette smoke (CS) exposure. The present study examined the effects of a potent Nox inhibitor and reactive oxygen species (ROS) scavenger, apocynin, on CS-induced muscle dysfunction. EXPERIMENTAL APPROACH Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks, with or without the coadministration of apocynin (5 mg·kg-1 , i.p.). C2C12 myotubes exposed to either hydrogen peroxide (H2 O2 ) or water-soluble cigarette smoke extract (CSE) with or without apocynin (500 nM) were used as an experimental model in vitro. KEY RESULTS Eight weeks of CS exposure caused muscle dysfunction in mice, reflected by 10% loss of muscle mass and 54% loss of strength of tibialis anterior which were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H2 O2 or CSE caused myofibre wasting, accompanied by ~50% loss of muscle-derived insulin-like growth factor (IGF)-1 and two-fold induction of Cybb, independent of cellular inflammation. Expression of myostatin and MAFbx, negative regulators of muscle mass, were up-regulated under H2 O2 but not CSE conditions. Apocynin treatment abolished CSE-induced Cybb expression, preserving muscle-derived IGF-1 expression and signalling pathway downstream of mammalian target of rapamycin (mTOR), thereby preventing myofibre wasting. CONCLUSION AND IMPLICATIONS Targeted pharmacological inhibition of Nox-derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Inflammation
Myostatin
chronic obstructive pulmonary disease
Cigarette Smoking
protein carbonylation
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Internal medicine
Smoke
Medicine
Animals
CYBB
Muscle, Skeletal
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
Mice, Inbred BALB C
NADPH oxidase
biology
business.industry
Myogenesis
Skeletal muscle
Acetophenones
Research Papers
030104 developmental biology
Endocrinology
medicine.anatomical_structure
antioxidants
chemistry
Apocynin
biology.protein
IGF‐1
medicine.symptom
business
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 14765381 and 00071188
- Volume :
- 178
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- British Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....f108aaf8fa7f30a898b7c66d50510429