ACIDOSIS AND GLUCOCORTICOIDS INTERACT TO PROVOKE MUSCLE PROTEIN AND AMINO-ACID CATABOLISM

被引：10

作者：

ENGLAND, BK

PRICE, SR

机构：

[1] Renal Division Emory University School of Medicine, Atlanta, GA

来源：

BLOOD PURIFICATION | 1995年 / 13卷 / 3-4期

关键词：

ACIDOSIS; CHRONIC RENAL FAILURE; PROTEIN DEGRADATION; BRANCHED-CHAIN AMINO ACIDS; BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE; UBIQUITIN; PROTEASOME; GLUCOCORTICOIDS;

D O I：

10.1159/000170197

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Malnutrition and a loss of lean body mass frequently complicate chronic renal failure. Muscle wasting in uremia is caused by increased protein degradation, decreased protein synthesis and increased branched-chain amino acid oxidation. Acidosis and glucocorticoids are pivotal in these pathophysiologic aberrations. When the acidosis of chronic renal failure is corrected by feeding bicarbonate, protein degradation and amino acid oxidation normalize. Likewise, if patients and animals with normal renal function are made acidotic, protein degradation and amino acid oxidation increase. In adrenalectomized, acidotic rats, proteolysis increases only when they are supplemented with physiologic concentrations of glucocorticoids, suggesting that glucocorticoids are necessary for increased proteolysis. Acidosis stimulates the ATP-dependent proteolytic process involving ubiquitin and the 26S proteasome. Thus, acidosis evokes a glucocorticoid-dependent catabolic response in muscle that can account for the protein wasting associated with uremia.

引用

页码：147 / 152

页数：6

共 26 条

[1]

San Pietro A., Rittcnberg D., A study of the rate of protein synthesis in humans. II. Measurement of the metabolic pool and the rate of protein synthesis, J Biol Chem, 201, pp. 457-473, (1953)

[2]

Mitch W.E., Clark A.S., Specificity of the effects of leucine and its metabolites on protein degradation in skeletal muscle, Biochem J, 222, pp. 579-586, (1984)

[3]

Nair K.S., Schwartz R.G., Welle S., Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans, Am J Phvsiol, 263, pp. E928-E934, (1992)

[4]

Mitch W.E., May R.C., Clark A.S., Maroni B.J., Kelly R.A., Influence of insulin resistance and amino acid supply on muscle protein turnover in uremia, Kidney Int, 32, pp. 104-108, (1987)

[5]

Sartorius O.W., Roemmelt J.C., Pitts R.F., The renal regulation of acid- base balance in man. IV. The nature of the renal compensation in ammonium chloride acidosis, J Clin Invest, 28, pp. 423-439, (1949)

[6]

May R.C., Kelly R.A., M Itch W.E., Met-abolic acidosis stimulates protein degradation in rat muscle by a gluco-corticoid-dependent mechanism, J Clin Invest, 77, pp. 614-621, (1986)

[7]

Lyon D.M., Dunlop D.M., Stewart C.P., The alkaline treatment of chronic nephritis, Lancet, pp. 1009-1013, (1931)

[8]

McSherry E., Morris R.C., Attainment of normal stature with alkali therapy in infants and children with classic renal tubular acidosis, J Clin Invest, 61, pp. 509-514, (1978)

[9]

May R.C., Kelly R.A., Mitch W.E., Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis, J Clin Invest, 79, pp. 1099-1103, (1987)

[10]

Harper A.E., Miller R.H., Block K.P., Branched-chain amino acid metabolism, Annu Rev Nutr, 4, pp. 409-454, (1984)

← 1 2 3 →