Apocynin prevents cigarette smoking‐induced loss of skeletal muscle mass and function in mice by preserving proteostatic signalling
Male
0301 basic medicine
Mice, Inbred BALB C
0303 health sciences
610
Acetophenones
Research Papers
Cigarette Smoking
3. Good health
Mice
03 medical and health sciences
Smoke
616
Animals
Muscle, Skeletal
DOI:
10.1111/bph.15482
Publication Date:
2021-04-05T05:44:52Z
AUTHORS (11)
ABSTRACT
Background and PurposeSkeletal 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 ApproachMale 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 (H2O2) or water‐soluble cigarette smoke extract (CSE) with or without apocynin (500 nM) were used as an experimental model in vitro.Key ResultsEight 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 H2O2 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 H2O2 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 ImplicationsTargeted pharmacological inhibition of Nox‐derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.
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CITATIONS (12)
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