Myofibrillar protein and gene expression in acute quadriplegic myopathy.
The dramatic muscle wasting, preferential loss of myosin and impaired muscle function in intensive care unit (ICU) patients with acute quadriplegic myopathy (AQM) have traditionally been suggested to be the result of proteolysis via specific proteolytic pathways. In this study we aim to investigate the mechanisms underlying the preferential loss of thick vs. thin filament proteins and the reassembly of the sarcomere during the recovery process in muscle samples from ICU patients with AQM. Quantitative and qualitative analyses of myofibrillar protein and mRNA expression were analyzed using SDS-PAGE, confocal microscopy, histochemistry and real-time PCR. The present results demonstrate that the transcriptional regulation of myofibrillar protein synthesis plays an important role in the loss of contractile proteins, as well as the recovery of protein levels during clinical improvement, myosin in particular, presumably in concert with proteolytic pathways, but the mechanisms are specific to the different thick and thin filament proteins studied.
Norman
Holly
H
Department of Clinical Neurophysiology, Uppsala University, Sweden.
Zackrisson
Håkan
H
Hedström
Yvette
Y
Andersson
Per
P
Nordquist
Jenny
J
Eriksson
Lars I
LI
Libelius
Rolf
R
Larsson
Lars
L
D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D011782:Quadriplegia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult; D000099163:Myosin Binding Protein C
D000199:Actins; D000251:Adenosine Triphosphatases; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D009218:Myosins; D012333:RNA, Messenger; D000099163:Myosin Binding Protein C