APOPTOSIS - A MECHANISM CONTRIBUTING TO REMODELING OF SKELETAL-MUSCLEIN RESPONSE TO HINDLIMB UNWEIGHTING

The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the preve ntion of muscle atrophy were examined. The number of nuclei demonstrat ing double-stranded DNA fragmentation seen by terminal deoxynucleotidy l transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double stain ing with TDT and antilaminin immunohistochemistry revealed that some T DT-positive nuclei were within the fiber lamina and were most likely m yonuclei. The number of fibers containing morphologically abnormal nuc lei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth f actor I (GH/IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (similar to 26%, P > 0.05) and significantly decre ased the number of fibers with morphologically abnormal nuclei. The da ta suggest that 1) ''programmed nuclear death'' contributes to the eli mination of myonuclei and/or satellite cells from atrophying fibers, a nd 2) GH/IGF-I administration plus muscle loading ameliorates the apop tosis associated with hindlimb unloading.