Protective effect of L-arginine administration on proteins of unloaded m. soleus

Abstract

Cytoskeletal and contractile proteins degenerate during functional unloading of muscle. The ratio of myosin heavy chain (MHC) expression changes simultaneously. We have supposed that NO can be a signal molecule related to the regulation of protein metabolism upon muscle unloading. To test this hypothesis, Wistar rats underwent functional unloading for 14 days without and with peroral administration of L-arginine (500 mg/kg) as NO precursor. Significant decreases in m. soleus mass, NO, nNOS, dystrophin, Hsp90, p-S6K, and type I MHC mRNA contents were found in the group of animals with unloading without preparation compared to those in control and in the group with unloading and administration of L-arginine; at the same time, increased contents of atrogin-1/MAFbx and MuRF-1 (p < 0.05) were found. No difference in the IGF-1 mRNA content between all three groups was found. Atrophy was significantly less pronounced in the group with unloading and L-arginine administration compared to that without the amino acid, and no destruction of cytoskeletal proteins was observed. We conclude that administration of L-arginine upon functional unloading decreases the extent of m. soleus atrophy, prevents the decrease in it of type I MHC mRNA, and blocks destructive changes in some cytoskeletal proteins. Such effect can be due to the absence of increase in this group of the content of some ubiquitin ligases and decreased intensity of the p70S6 kinase synthesis marker.

Various Jobs of Proteolytic Enzymes in Skeletal Muscle during Unloading: Facts and Speculations

“…These results are in agreement with recent data on calpastatin expression decrement under HS [39]. Interestingly, hypokinesia/hypogravity caused decrease of NO content leading to calpains inhibition [40]. At that, content of neuronal NO-synthase in soleus fibers under functional unloading decreased [41, 42].…”

“…We observed decrease of MuRF-1 and MAFbx expression in rat soleus under HS combined with application of NO donor, L-arginine. Evidently, experimental intensification of NO production inhibited ubiquitin ligases expression [40]. …”

Redox control of skeletal muscle atrophy

“…In contrast to the Suzuki et al findings [7], a recent study concludes that 14 days of hindlimb suspension results in a decrease in both muscle nNOS and NO levels [30]. Similarly, nitosative stress is not present in the rat diaphragm following 18 hours of inactivity due to prolonged mechanical ventilation [31].…”

Nitric Oxide, Sports Nutrition and Muscle Building

“…Although this work did not examine the involvement of satellite cells, it was shown that load-induced protein synthesis (as indicated by muscle mass) was inhibited in animals treated with a NOS inhibitor, indicating that NO plays a role in muscle protein synthesis. This study demonstrated that the decrease in myosin heavy chain type 1 associated with muscle unloading was diminished by the addition of arginine; however, this is likely a combination of alterations in protein synthesis and protein degradation found in unload-induced muscle atrophy [38,39]. Rather, the NOS-dependent component of the observed loadinduced hypertrophy was due to an increase in mRNA for both actin and type 1 myosin heavy chain, indicating that endogenous production of NO was involved in the increase in synthesis of contractile proteins.…”

“…Nitric oxide has been shown to be directly involved in muscle hypertrophy and fiber type transition observed in chronically loaded muscle in a rodent model [36]. Atrophy associated with functional unloading of muscle has been shown to be attenuated by the administration of arginine [38]. These authors went on to demonstrate that this NOS-dependence of the observed muscle hypertrophy was not due to an alteration of growth factor induction or activation/proliferation of satellite cells [37].…”