TY - JOUR
T1 - Muscle degradation in uremia
T2 - 3-Methylhistidine release in fed and fasted rats
AU - Li, J. B.
AU - Wassner, S. J.
N1 - Funding Information:
Discussion Postoperatively, growth in our uremic rats was significantly impaired and mean weights dropped to 80% of the control group. Although growth rates were equal 2 weeks after surgery, in keeping with their moderate uremia, the uremic rats were smaller and were actually gaining less weight than the sham- operated controls. Although our uremic rats excreted less creatinine per day (moles/l00 g body weight) suggesting a decrease in muscle mass, at least one muscle, the gastrocnemius, and the eviscerat-ed carcass contributed the same percentage of body weight in body groups. Because uremia is associated with a urinary 'creatinine deficit" due to increased gastrointestinal metabo- lism of creatinine [18], it is probable that the fraction of body weight present as muscle tissue was not significantly altered in the uremic group. Protein is the major nonaqueous component of muscle, and in the gastrocnemius, protein content averaged 18.5% out of the total of 25% dry weight. The slight increase in protein concen- tration during the first 24 hours of fasting has been observed previously and probably reflects a more rapid loss of other muscle components such as glycogen or triglycerides early in the course of starvation. In both groups, however, after 48 hours of starvation, protein concentration again equaled that of the fed state. Our finding that both muscle bound 3MH content and protein content were unchanged when measured in fed animals suggests that there was no decrease in the percentage of contractile muscle proteins in uremic rats. Some of the increased weight loss in uremic animals might be ascribable to dehydration, but the equality of protein concentra-tions, measured per gram of wet weight, suggests that the weight loss and decreased percentage of carcass to body weight reflected increased muscle catabolism in uremia. Numerous studies have appeared in which muscle protein degradation rates have been estimated from the urinary excre- tion of 3MH [3—7]. Although this may be adequate for animals or patients in a constant, unperturbed (for example, fed) state, our data demonstrate that different conclusions can be reached when serum and tissue concentrations are considered as well. For example, after 24 hours of fasting, there was a decrease in urinary 3MH excretion. When the total rate of release of 3MH from myofibrillar protein is taken into account, muscle degrada- tion rates were at least constant or perhaps even elevated, After 48 hours of fasting, urinary 3MH excretion increased but serum levels declined somewhat. If one assumes that serum concen- Acknowledgments This work was supported by a grant from the U.S. Public Health Service (#AM-24061). The authors thank Ms. J. Schlitzer and L. Hallman for their technical assistance, and Ms. J. flower for assistance in preparing this manuscript.
PY - 1981
Y1 - 1981
N2 - The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting, the uremic animals lost more weight (17.1%) than the shams (13.2%). The ratio of gastrocnemius muscle protein per gram of wet weight was not significantly different under any conditions. When fed and 48-hour fasted animals are compared, urinary excretion of 3MH rose from 0.81 to 1.32 moles per 24 hr per 100 g of initial body wt in shams and from 0.90 to 1.30 moles per 24 hr per 100 g of initial body wt in the uremics. When the ratio of 3MH to creatinine excretion in the urine was compared, there was no change in 3MH excretion between 0 and 24 hours, but there was an increase between 24 and 48 hours. Analysis of serum and muscle samples from red and 48-hour fasted animals revealed that the concentrations of 3MH increased in both groups during fasting, with the uremic rats having a larger increase in the total body 3MH pool. Myofibrillar degradation rates calculated from the sum of urinary excretion plus the changes in body 3MH pool size revealed that with moderate fasting, degradation rates increased in both sham and uremic rats with a larger increase being seen in the uremic group. After 48 hours of fasting, the increased amount of 3MH released from muscle of uremic rats was comparable to their larger percentage weight loss.
AB - The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting, the uremic animals lost more weight (17.1%) than the shams (13.2%). The ratio of gastrocnemius muscle protein per gram of wet weight was not significantly different under any conditions. When fed and 48-hour fasted animals are compared, urinary excretion of 3MH rose from 0.81 to 1.32 moles per 24 hr per 100 g of initial body wt in shams and from 0.90 to 1.30 moles per 24 hr per 100 g of initial body wt in the uremics. When the ratio of 3MH to creatinine excretion in the urine was compared, there was no change in 3MH excretion between 0 and 24 hours, but there was an increase between 24 and 48 hours. Analysis of serum and muscle samples from red and 48-hour fasted animals revealed that the concentrations of 3MH increased in both groups during fasting, with the uremic rats having a larger increase in the total body 3MH pool. Myofibrillar degradation rates calculated from the sum of urinary excretion plus the changes in body 3MH pool size revealed that with moderate fasting, degradation rates increased in both sham and uremic rats with a larger increase being seen in the uremic group. After 48 hours of fasting, the increased amount of 3MH released from muscle of uremic rats was comparable to their larger percentage weight loss.
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U2 - 10.1038/ki.1981.141
DO - 10.1038/ki.1981.141
M3 - Article
C2 - 7300120
AN - SCOPUS:0019805189
SN - 0085-2538
VL - 20
SP - 321
EP - 325
JO - Kidney International
JF - Kidney International
IS - 3
ER -