Regulation of myosin heavy chain gene expression after short-term diaphragm inactivation.
Although prolonged diaphragm denervation (DNV) produces myofiber atrophy and a loss of type I myosin heavy chain (MHC) expression, short-term DNV leads to significant diaphragm hypertrophy. The purpose of this study was to explore the regulation of MHC isoform expression and muscle remodeling during DNV hypertrophy of the diaphragm. Both unilateral and bilateral DNV led to similar changes, with a significant increase in total RNA content and muscle mass but no change in dry-to-wet weight ratio. Sarcomere number was also increased in diaphragm myofibers after DNV ( approximately 20%), suggesting an adaptive response to muscle stretch. There was hypertrophy of type I myofibers and increased coexpression of type I and type II MHCs within single myofibers by immunocytochemistry as well as increased type I MHC (25-46%) and decreased type IIb MHC (14-39%) by SDS-PAGE. Contractility parameters were also consistent with a type II-to-type I MHC phenotype transformation. Importantly, DNV-induced modulation of MHC isoform mRNA transcript levels did not correspond to changes in their cognate proteins, suggesting a major degree of posttranscriptional control. We conclude that DNV hypertrophy of the diaphragm is associated with reciprocal changes in type I and type II MHC isoforms that are directly opposed to the type I-to-type II MHC phenotype transformation reported in the diaphragm DNV atrophy model. Furthermore, in contradistinction to most hypertrophy models, control of MHC gene expression and myofibrillar remodeling after short-term DNV appears to entail major involvement of posttranscriptional regulatory mechanisms.
Yang
L
L
Respiratory Division, McGill University Health Centre, Montreal, Quebec H3A 1A1.
Bourdon
J
J
Gottfried
S B
SB
Zin
W A
WA
Petrof
B J
BJ
D000818:Animals; D015152:Blotting, Northern; D003964:Diaphragm / Q000294:innervation* / Q000473:pathology / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction; D009121:Muscle Denervation; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000473:pathology
D012333:RNA, Messenger; D018995:Myosin Heavy Chains