IMMOBILIZATION DIFFERENTIALLY ALTERS HUMAN TYPE I, IIa, AND IIx MHC mRNA ISOFORMS 386

Abstract

Mechanical loading (Caiozzo et al. JAP 80:1503, 1996) or unloading (Caiozzo et al. JAP 81:123, 1996) of animal and human (Fry et al. EJAP 68:246, 1994) skeletal muscle results in isoform shifts of myosin heavy-chain (MHC) proteins. Occasionally alterations in MHC proteins are uncoupled from changes in MHC mRNAs. As an initial effort to better characterize the cellular mechanism of human skeletal muscle atrophy, the effect of immobilization was investigated on MHC mRNA isoform expression. Sedentary healthy young men's(n=24) and women's (n=24) left legs were immobilized for 3 weeks. Before and after immobilization the quadriceps muscle was tested for peak isometric and isokinetic eccentric and concentric (60°/s) force and type I, IIa, and IIx MHC mRNA isoform expression from biopsy samples of the vastus lateralis. Immobilization reduced voluntary strength 41% (±SD 12%) and histochemically determined type I and II muscle fiber size 12% (±4%)(both p <.05). Compared to baseline (0.0094±0.0044 μg/ml/mg ww), total RNA (n=22) did not change with immobilization (0.0086±0.0031μg/ml/mg ww, p > 0.05). Ribonuclease protection assay-derived type I MHC mRNA isoform was significantly downregulated by immobilization to 0.72(±0.2) of baseline (p <.05). Type IIa MHC mRNA isoform was not altered (1.1-fold [±0.3] change), while type IIx MHC mRNA isoform was significantly 2.9-fold (±1.7) upregulated (p <.05). These data suggest that while histochemically both major fiber types atrophied, immobilization differentially altered type I, IIa, and IIx MHC mRNA isoform expression.