Myosin loss in denervated rat soleus muscle after dexamethasone treatment.
OBJECTIVE
Critical illness myopathy (CIM) is an acute myopathy that appears in the setting of critical illness or during exposure to corticosteroids and neuromuscular blocking agents. Its pathological feature is selective loss of thick myosin filaments. Our aim is to gain further insight into the pathomechanism of myosin loss in this myopathy.


METHODS
To clarify the expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after saline and dexamethasone treatments.


RESULTS
Denervated muscles from dexamethasone-treated rats showed marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was significantly increased in denervated dexamethasone-treated muscles, suggesting that the ubiquitin-proteasome pathway plays an important role in muscular wasting in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in the denervated dexamethasone-treated muscles.


CONCLUSIONS
Our findings suggest that an altered transcription rate of myosin, as well as the upregulation of multiple ubiquitin ligases, may be responsible for selective myosin loss in this myopathy.
Horinouchi
Hideo
H
Division of Neurology and Neuromuscular Disorders, Department of Brain and Nerve Science, Oita University Faculty of Medicine, Oita, Japan. horinouc@oita-med.ac.jp
Kumamoto
Toshihide
T
Kimura
Noriyuki
N
Ueyama
Hidetsugu
H
Tsuda
Tomiyasu
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008297:Male; D009121:Muscle Denervation; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis* / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics
D009124:Muscle Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D018995:Myosin Heavy Chains