The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans

Abstract

To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF-linked (RhoA, RhoGDI, STARS and SRF), myostatin-linked (myostatin, Smad2, Smad3 and FLRG) and Foxo-linked (P-Akt, Foxo1, Foxo3a and Atrogin-1) mediators. A single lower limb of each of eight healthy men was suspended for 20 days. Biopsy specimens were obtained from the vastus lateralis muscle pre- and post-suspension. The volume of the vastus lateralis muscle was significantly decreased after unloading. The amount of RhoA, RhoGDI or SRF protein in the muscle was not significantly changed post-suspension. An RT-PCR semiquantitative analysis showed increased levels of myostatin mRNA but not Smad2, Smad3 or FLRG mRNA. Unloading did not elicit significant changes in the amount of p-Smad3 or myostatin protein in the muscle. The amount of p-Akt protein was markedly reduced in the unloaded muscle. Lower limb SUSPENSION DID NOT INFLUENCE THE EXPRESSION PATTERN OF FOXO1, FOXO3A OR ATROGIN-1. Unloading inducing a mild degree of muscle atrophy may decrease p-Akt and increase myostatin but not SRF-linked mediators.