The activation of apoptosis factor in hindlimb unloading-induced muscle atrophy under normal and low-temperature environmental conditions.
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.
Nagano
Katsuhito
K
Division of Clinical Pharmacotherapeutics, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan. nagano@xg8.so-net.ne.jp
Suzaki
Etuko
E
Nagano
Yumi
Y
Kataoka
Katsuko
K
Ozawa
Koichiro
K
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
D051033:Apoptosis Inducing Factor; D053148:Caspase 3