Bed rest increases the amount of mismatched fibers in human skeletal muscle

The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expr ession on both mRNA and protein level in human skeletal muscle fibers were studied. Muscle biopsies from vastus lateralis muscle were obtained from se ven healthy young male subjects before and after the bed-rest period. Combi ned in situ hybridization, immunocytochemistry, and ATPase histochemistry a nalysis of serial sections of the muscle biopsies demonstrated that fibers showing a mismatch between MHC isoforms at the mRNA and protein level incre ased significantly after the bed-rest period, suggesting an increase in the amount of muscle fibers in a transitional state. Accordingly fibers showin g a match in expression of MHC-1 and of MHC-2A at the mRNA and protein leve l decreased, whereas fibers showing a match between MHC-2X mRNA and protein increased after bed rest. Overall, there was an increase in fibers in a tr ansitional state from phenotypic type 1 --> 2A and 2A --> 2X. Furthermore, a number of fibers with unusual MHC mRNA and isoprotein combinations were o bserved after bed rest (e.g., type 1 fibers with only mRNA for 2X and type 1 fibers negative for mRNA for MHC-beta/slow, 2A, and 2X). In contrast, no changes were revealed after an examination at the protein level alone. Thes e data suggest that the reduced load-bearing activity imposed on the skelet al muscles through bed rest will alter MHC gene expression, resulting in co mbinations of mRNA and MHC isoforms normally not (or only rarely) observed in muscles subjected to load-bearing activity. On the other hand, the prese nt data also show that 37 days of bed rest are not a sufficient stimulus to induce a similar change at the protein level, as was observed at the gene level.