The posterior cricoarytenoid muscle is spared from MuRF1-mediated muscle atrophy in mice with acute lung injury.
BACKGROUND
Skeletal muscle wasting in acute lung injury (ALI) patients increases the morbidity and mortality associated with this critical illness. The contribution of laryngeal muscle wasting to these outcomes is unknown, though voice impairments and aspiration are common in intensive care unit (ICU) survivors. We evaluated the intrinsic laryngeal abductor (PCA, posterior cricoarytenoid), adductor (CT, cricothyroid) and limb (EDL, extensor digitorum longus) muscles in a mouse model of ALI.


METHODS
Escherichia coli lipopolysaccharides were instilled into the lungs of adult male C57Bl6J mice (ALI mice). Limb and intrinsic laryngeal muscles were analyzed for fiber size, type, protein expression and myosin heavy chain (MyHC) composition by SDS-PAGE and mass spectroscopy.


RESULTS
Marked muscle atrophy occurred in the CT and EDL muscles, while the PCA was spared. The E3 ubiquitin ligase muscle ring finger-1 protein (MuRF1), a known mediator of limb muscle atrophy in this model, was upregulated in the CT and EDL, but not in the PCA. Genetic inhibition of MuRF1 protected the CT and EDL from ALI-induced muscle atrophy. MyHC-Extraocular (MyHC-EO) comprised 27% of the total MyHC in the PCA, distributed as hybrid fibers throughout 72% of PCA muscle fibers.


CONCLUSIONS
The vocal cord abductor (PCA) contains a large proportion of fibers expressing MyHC-EO and is spared from muscle atrophy in ALI mice. The lack of MuRF1 expression in the PCA suggests a previously unrecognized mechanism whereby this muscle is spared from atrophy. Atrophy of the vocal cord adductor (CT) may contribute to the impaired voice and increased aspiration observed in ICU survivors. Further evaluation of the sparing of muscles involved in systemic wasting diseases may lead to potential therapeutic targets for these illnesses.
Internal Medicine-Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America ; Wake Forest Critical Care Translational Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
D Clark
DC
Files
Department of Medicine, Duke University, Durham, North Carolina, United States of America.
Kunhong
K
Xiao
Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Tan
T
Zhang
Internal Medicine-Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Chun
C
Liu
Department of Medicine, Duke University, Durham, North Carolina, United States of America.
Jiang
J
Qian
Department of Radiation Oncology and Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Weiling
W
Zhao
Internal Medicine-Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America ; Wake Forest Critical Care Translational Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Peter E
PE
Morris
Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Osvaldo
O
Delbono
Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Xin
X
Feng
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D007821:Laryngeal Muscles / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009133:Muscular Atrophy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014827:Vocal Cords / Q000378:metabolism / Q000473:pathology; D019282:Wasting Syndrome / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D008070:Lipopolysaccharides; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases