We studied glucocorticoid-induced muscle wasting and subsequent recovery in adult (7-mo-old) and old (22-mo-old) rats, since the increased incidence of various disease states may result in glucocorticoids hypersecretion in aging. Adult and old rats received dexamethasone in their drinking water and were then allowed to recover. Muscle wasting occurred more rapidly in old rats and the recovery of muscle mass was impaired, suggesting that glucocorticoids may be involved in the emergence of muscle atrophy with advancing age. According to measurements in incubated epitrochlearis muscles, dexamethasone-induced muscle wasting mainly resulted from increased protein breakdown in the adult, but from depressed protein synthesis in the aged animal. Increased expression of cathepsin D, m-calpain, and ubiquitin was observed in the muscles from both dexamethasonetreated adult and old rats. By contrast, the disappearance of the stimulatory effect of glucocorticoids on protein breakdown in aging occurred along with a loss of ability of steroids to enhance the expression of the 14-kD ubiquitin carrier protein E2, which is involved in protein substrates ubiquitinylation, and of subunits of the 20 S proteasome (the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates). Thus, if glucocorticoids play any role in the progressive muscle atrophy seen in aging, this is unlikely to result from an activation of the ubiquitin-proteasome proteolytic pathway. (J. Cln.
This study was carried out to analyse glucocorticoid-induced muscle wasting and subsequent recovery in adult (6-8 months) and old (18-24 months) rats because the increased incidence of various disease states results in hypersecretion of glucocorticoids in ageing. Adult and old rats received dexamethasone in their drinking water for 5 or 6 d and were then allowed to recover for 3 or 7 d. As dexamethasone decreased food intake, all groups were pair-fed to dexamethasonetreated old rats (i.e. the group that had the lowest food intake). At the end of the treatment, adult and old rats showed significant increases in blood glucose and plasma insulin concentrations. This increase disappeared during the recovery period. Protein synthesis of different muscles was assessed in vivo by a flooding dose of [13C]valine injected subcutaneously 50 min before slaughter. Dexamethasone induced a significant decrease in protein synthesis in fast-twitch glycolytic and oxidative glycolytic muscles (gastrocnemius, tibialis anterior, extensor digitorum longus). The treatment affected mostly ribosomal efficiency. Adult dexamethasone-treated rats showed an increase in protein synthesis compared with their pair-fed controls during the recovery period whereas old rats did not. Dexamethasone also significantly decreased protein synthesis in the predominantly oxidative soleus muscle but only in old rats, and increased protein synthesis in the heart of adult but not of old rats. Thus, in skeletal muscle, the catabolic effect of dexamethasone is maintained or amplified during ageing whereas the anabolic effect in heart is depressed. These results are consistent with muscle atrophy occurring with ageing.
This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin-and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25·9 and 58·1% respectively. In old rats, this effect was even greater, being 49·3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoidinduced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.
It has been suggested that protein synthesis in peripheral tissues: (1) responds in a curvilinear manner to increasing feed intake over a wide range of feeding levels; and (2) has a greater sensitivity to intake than protein breakdown. The aim of the present experiment was to test these hypotheses across the ovine hindlimb. Six growing sheep (6 -8 months, 30 -35 kg), with catheters in the aorta (two), posterior vena cava and jugular vein, received each of four intakes of dried grass pellets (0 : 5, 1 : 0, 1 : 5 and 2 : 5 Â maintenance energy; M) for a minimum of 7 d. A U-13 C-labelled algal hydrolysate was infused intravenously for 10 h and from 3 -9 h para-aminohippuric acid was infused to measure plasma flow. Arterial and venous plasma were obtained over the last 4 h and the concentrations and enrichments of thirteen 13 C-labelled amino acids (AA) were determined by GC -MS. As intake increased, a positive linear response was found for plasma flow, arterial concentrations of the aromatic and branched-chain AA, total flow of all AA into the hindquarters and net mass balance across the hindquarters (except glycine and alanine). Based on two separate statistical analyses, the data for protein synthesis showed a significant linear effect with intake (except for phenylalanine, glycine and alanine). No significant curvilinear effect was found, which tends not to support hypothesis 1. Nonetheless, protein synthesis was not significantly different between 0 : 5, 1 : 0 and 1 : 5 Â M and thus the 2 : 5 Â M intake level was largely responsible for the linear relationship found. There was no significant response in protein breakdown to intake, which supports hypothesis 2.
Volatile compounds from tomatoes were measured in the headspace above tomatoes and in the air expired from the noses of people eating tomatoes (nosespace). Eleven target compounds, representative of the different metabolic pathways that contribute to tomato aroma were chosen for analysis. The procedure consisted of trapping volumes of headspace or nosespace on Tenax, desorbing and chromatographing the samples on gas chromatographs and quantification by integration of characteristic ion chromatograms. Small volumes (8.5 cm3) of headspace were used to develop the method which was then applied to study potential sources of variation in the raw material and in the sampling procedure. The variation in headspace profiles, with time after dicing tomatoes, and with tissue maturity, demonstrated that the amounts of some volatiles changed with time and with maturity. Sampling was therefore undertaken using batches of tomatoes with similar histories and the time of sampling was fixed. The headspace and nosespace profiles from tomatoes produced raw data with substantial variation (percentage coeficient of variation 50-60%) but this appeared to be due to different amounts of volatiles in the replicates. When data were expressed on a relative basis by normalisation, the profiles from groups of replicates were seen to be quite similar for nine of the compounds but values for 3-methylnitrobutane and 2-isobutylthiazole showed considerable variation. Nosespace profiles of tomato volatiles were broadly similar between operators when expressed on a relative basis; the actual total amounts varied considerably. The headspace profiles from diced and stomached tomatoes were comparable but distinctly different from the nosespace profile. There were differences between the headspace and nosespace profiles particularly in the amounts of 3-methylbutanal, dimethyl disulphide and hexanal which were present to a greater extent in the headspace on a relative basis.
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