title: The activation of apoptosis factor in hindlimb unloading-induced muscle atrophy under normal and low-temperature environmental conditions.
abstract: In order to identify the apoptosis-induced factors and apoptosis pathway in hindlimb unloading muscle atrophy, the reciprocal relationships between caspase-3 activation and factors related to mitochondria, other organelle pathways, oxidative stress and nitric oxide were investigated. Male Wistar rats were divided into four groups, two groups of hindlimb-unloaded rats were maintained under normal (25 degrees C) and low-temperature (10 degrees C) environmental conditions for a 3-week experimental period, plus two corresponding control groups. Active caspase-3-containing myofibers were observed in the hindlimb-unloaded rats in normal and low-temperature environments, but not in the control rats. In these caspase-3-containing fibers, DNA fragmentation, dystrophin breakdown, increased immunolabeling of mu-calpain, decreased cytochrome c, cathepsin-D effusion from the lysosomes and increased lipid peroxidation were observed, while no changes in active caspase-12, eNOS or nNOS immunolabeling were seen. Furthermore, although caspase-3 activation was observed in type-I fibers, caspase-12 labeling was observed in fibers of the hybrid type. These results show that the apoptosis observed in hindlimb unloading-induced muscle atrophy is caused by activation of the caspase cascade via the lysosome pathway. Moreover, the results suggest that caspase-12 does not activate caspase-3 due to differences in the cell differentiation or the apoptosis-inducing stimulation.
authors.affiliation: Division of Clinical Pharmacotherapeutics, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan. nagano@xg8.so-net.ne.jp
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Nagano
authors.forename: Etuko
authors.initials: E
authors.lastname: Suzaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nagano
authors.forename: Katsuko
authors.initials: K
authors.lastname: Kataoka
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D003080:Cold Temperature; D053938:DNA Fragmentation; D006614:Hindlimb / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D020966:Muscular Disorders, Atrophic / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D016474:Weight-Bearing
chemical_list: D051033:Apoptosis Inducing Factor; D053148:Caspase 3