Effect of 3-hydroxy-3-methylbutyrate [HMB] on muscle cathepsins and calpain activities during the post-dexamethasone recovery period in young rats
This study was conducted to assess the effect of the leucine metabolite, 3-hydroxy-3-methylbutyrate (HMB) on animal performance, and also cathepsins and calpain II activities in the gastrocnemius muscle in young rats undergoing dexamethasone (DX) treatment and subsequent recovery. Five days of DX administration resulted in an increase in calpain activity. During 5 days of recovery alone, calpain activity was still elevated whereas HMB treatment decreased calpain activity to the values observed in the control group. DX treatment increased the total lysosomal proteolytic activity. HMB administration during the recovery period accelerated return of the proteolytic enzymes activity to the control values. The use of selective inhibitors of thiol and aspartic cathepsins (leupeptin and pepstatin, respectively) allowed us to determine the type of cathepsin responsible for the DX-induced proteolysis observed. Since DX treatment decreased cathepsin D activity (which returned to the control values during recovery) it is assumed that thiol cathepsins are involved in the increase of lysosomal proteolysis observed. We have demonstrated that lysosomal and Ca+2-dependent proteinases involved in myofibryllar protein degradation differ in their activity due to DX treatment. It has been concluded that HMB modifies muscle proteolysis through changes in the activity of the proteolytic enzymes. Practical applications of this phenomenon are discussed.