title: Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting.
abstract: The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the prevention of muscle atrophy were examined. The number of nuclei demonstrating double-stranded DNA fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double staining with TDT and antilaminin immunohistochemistry revealed that some TDT-positive nuclei were within the fiber lamina and were most likely myonuclei. The number of fibers containing morphologically abnormal nuclei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (approximately 26%, P > 0.05) and significantly decreased the number of fibers with morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear death" contributes to the elimination of myonuclei and/or satellite cells from atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates the apoptosis associated with hindlimb unloading.
authors.affiliation: Department of Physiological Science, University of California, Los Angeles 90095-1527, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Allen
authors.forename: J K
authors.initials: JK
authors.lastname: Linderman
authors.forename: R R
authors.initials: RR
authors.lastname: Roy
authors.forename: A J
authors.initials: AJ
authors.lastname: Bigbee
authors.forename: R E
authors.initials: RE
authors.lastname: Grindeland
authors.forename: V
authors.initials: V
authors.lastname: Mukku
authors.forename: V R
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D006614:Hindlimb / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016474:Weight-Bearing
chemical_list: D007334:Insulin-Like Growth Factor I