Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats.

BACKGROUND: It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear. METHODS: Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated. RESULTS: Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion. CONCLUSION: The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling.

Effects of dimethyl sulphoxide and dexamethasone on mRNA expression of myogenesis- and muscle proteolytic system-related genes in mouse myoblastic C2C12 cells.

We examined the time course of mRNA expression of myogenic cell differentiation- and muscle proteolytic system-related genes in cultures of C2C12 cells during differentiation from myoblasts to myotubes. Furthermore, we treated C2C12 myotubes with dimethyl sulphoxide (DMSO) and dexamethasone (Dex), and examined changes in these mRNA levels. Myogenin (Myog), Atrogin1, forkhead box O1 (Foxo1) and Capn1 mRNA levels increased in C2C12 cells differentiating from myoblasts to myotubes, whereas Myf5 mRNA levels decreased. Although genes such as MRF4, Foxo3a, UbB, Capn1 and MuRF1 mRNAs in the myotubes were affected by DMSO exposure, mRNA levels of other genes were not markedly affected by exposure to 0.02% or 0.5% DMSO. Myf5, MRF4, Atrogin1, Foxo3 and MuRF1 mRNA levels were elevated by Dex at all time points, Cbl and Capn1 mRNA levels were significantly elevated by Dex at 8 h, and Myog mRNA levels were significantly elevated by Dex at 24 h. However, CtsH mRNA levels decreased significantly with Dex at 24 h. This study provides a useful database of gene profiles that are differentially expressed throughout myogenic cell differentiation and the muscle proteolytic system.

Enhancement of myofibrillar proteolysis following infusion of amino acid mixture correlates positively with elevation of core body temperature in rats.

Administration of an amino acid (AA) mixture stimulates muscle protein synthesis and elevates core body temperature (T(b)), as characteristically found under anesthetic conditions. We tested the hypothesis that not only AA given, but also AA produced by degradation of endogenous muscular protein are provided for muscle protein synthesis, which is further reflected in T(b) modifications. Rats were intravenously administered an AA mixture or saline in combination with the anesthetic propofol or lipid emulsion. We measured plasma 3-methylhistidine (MeHis) concentrations as an index of myofibrillar protein degradation, rectal temperature and mRNA expression of atrogin-1, MuRF-1 and ubiquitin in gastrocnemius and soleus muscles of rats following 3 h infusion of test solutions. T(b) did not differ significantly between conscious groups, but was higher in the AA group than in the saline group among anesthetized rats. Plasma MeHis concentrations were higher in the AA group than in the saline group under both conditions. Plasma MeHis levels correlated positively with T(b) of rats under both conditions. AA administration decreased mRNA levels of atrogin-1 and ubiquitin in gastrocnemius muscle and all mRNA levels in soleus muscle. These results suggest that AA administration enhances myofibrillar protein degradation and that the change is a determinant of T(b) modification by AA administration. However, the mechanisms underlying AA administration-associated enhancement of myofibrillar proteolysis remains yet to be determined.