Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1977 May;59(5):869–878. doi: 10.1172/JCI108709

Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver.

S B Grossman, S H Yap, D A Shafritz
PMCID: PMC372295  PMID: 856871

Abstract

Chronic renal failure in rats leads to changes in hepatic protein synthesis and albumin metabolism at both the cellular and molecular level. In rats with chronic uremia (blood urea nitrogen greater than 45 mg/100 ml 1 mo after surgical reduction in renal mass), cell-free protein synthesis is reduced 30--40% in liver membrane-bound polyribosomes. Albumin synthesis by membrane-bound polysomes in uremia is reduced even more than the reduction in total protein synthesis. Activity of free polysomes remains norma. There is also intracellular accumulation of albumin in liver of uremic rats and a concomitant decrease in serum albumin. In normal liver, most intracellular albumin is located in the microsomal fraction, whereas in liver from uremic animals the excess albumin is found in the free cytosol fraction. These results can be explained either by a defect in synthesis of albumin by membrane-bound polysomes with release of newly synthesized albumin into the cytosol or by a reduced ability of polysomes synthesizing albumin to associate with the membrane fraction in rats with chronic renal failure.

Full text

PDF
869

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLAHD W. H., FIELDS M., GOLDMAN R. The turnover rate of serum albumin in the nephrotic syndrome as determined by I 131-labeled albumin. J Lab Clin Med. 1955 Nov;46(5):747–756. [PubMed] [Google Scholar]
  2. BRICKER N. S., KLAHR S., RIESELBACH R. E. THE FUNCTIONAL ADAPTATION OF THE DISEASED KIDNEY. I. GLOMERULAR FILTRATION RATE. J Clin Invest. 1964 Oct;43:1915–1921. doi: 10.1172/JCI105065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baliga B. S., Pronczuk A. W., Munro H. N. Regulation of polysome aggregation in a cell-free system through amino acid supply. J Mol Biol. 1968 Jul 14;34(2):199–218. doi: 10.1016/0022-2836(68)90247-7. [DOI] [PubMed] [Google Scholar]
  4. Bianchi R., Mariani G., Pilo A. Albumin synthesis measurement by means of an improved two tracer method in patients with chronic renal failure. Effects of low protein diet. J Nucl Biol Med. 1970 Oct-Dec;14(4):136–144. [PubMed] [Google Scholar]
  5. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blobel G., Dobberstein B. Transfer of proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J Cell Biol. 1975 Dec;67(3):852–862. doi: 10.1083/jcb.67.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CAMPBELL P. N., STONE N. E. The synthesis of serum albumin and tissue proteins in slices of rat liver and liver tumour. Biochem J. 1957 May;66(1):19–31. doi: 10.1042/bj0660019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coles G. A., Peters D. K., Jones J. H. Albumin metabolism in chronic renal failure. Clin Sci. 1970 Sep;39(3):423–435. doi: 10.1042/cs0390423. [DOI] [PubMed] [Google Scholar]
  9. Crane L. J., Miller D. L. A solid-phase radioimmunoassay for fibrinogen. Anal Biochem. 1975 Mar;64(1):60–67. doi: 10.1016/0003-2697(75)90404-2. [DOI] [PubMed] [Google Scholar]
  10. DRABKIN D. L., MARSH J. B. Metabolic channeling in experimental nephrosis. I. Protein and carbohydrate metabolism. J Biol Chem. 1955 Feb;212(2):623–631. [PubMed] [Google Scholar]
  11. Dorling P. R., Quinn P. S., Judah J. D. Evidence for the coupling of biosynthesis and secretion of serum albumin in the rat. The effect of colchicine on albumin production. Biochem J. 1975 Nov;152(2):341–348. doi: 10.1042/bj1520341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fleck A., Shepherd J., Munro H. N. Protein synthesis in rat liver: influence of amino acids in diet on microsomes and polysomes. Science. 1965 Oct 29;150(3696):628–629. doi: 10.1126/science.150.3696.628. [DOI] [PubMed] [Google Scholar]
  13. GITLIN D., JANEWAY C. A., FARR L. E. Studies on the metabolism of plasma proteins in the nephrotic syndrome. I. Albumin, gamma-globulin and iron-binding globulin. J Clin Invest. 1956 Jan;35(1):44–56. doi: 10.1172/JCI103251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. JARNUM S. Fecal 131-I-output after intravenous injection of 131-I-labelled human serum albumin in normo- and hypoproteinemic subjects. Scand J Clin Lab Invest. 1961;13:462–475. doi: 10.1080/00365516109137311. [DOI] [PubMed] [Google Scholar]
  15. Jensen H., Rossing N., Andersen S. B., Jarnum S. Albumin metabolism in the nephrotic syndrome in adults. Clin Sci. 1967 Dec;33(3):445–457. [PubMed] [Google Scholar]
  16. KATZ J., BONORRIS G., SELLERS A. L. ALBUMIN METABOLISM IN AMINONUCLEOSIDE NEPHROTIC RATS. J Lab Clin Med. 1963 Dec;62:910–934. [PubMed] [Google Scholar]
  17. KATZ J., ROSENFELD S., SELLERS A. L. Role of the kidney in plasma albumin catabolism. Am J Physiol. 1960 Apr;198:814–818. doi: 10.1152/ajplegacy.1960.198.4.814. [DOI] [PubMed] [Google Scholar]
  18. KELLEY V. C., ZIEGLER M. R., DOEDEN D., McQUARRIE I. Labeled methionine as an indicator of protein formation in children with lipoid nephrosis. Proc Soc Exp Biol Med. 1950 Oct;75(1):153–155. doi: 10.3181/00379727-75-18128. [DOI] [PubMed] [Google Scholar]
  19. Katz J., Bonorris G., Okuyama S., Sellers A. L. Albumin synthesis in perfused liver of normal and nephrotic rats. Am J Physiol. 1967 Jun;212(6):1255–1260. doi: 10.1152/ajplegacy.1967.212.6.1255. [DOI] [PubMed] [Google Scholar]
  20. Kelman L., Saunders S. J., Wicht S., Frith L., Corrigall A., Kirsch R. E., Terblanche J. The effects of amino acids on albumin synthesis by the isolated perfused rat liver. Biochem J. 1972 Oct;129(4):805–809. doi: 10.1042/bj1290805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kemper B., Habener J. F., Mulligan R. C., Potts J. T., Jr, Rich A. Pre-proparathyroid hormone: a direct translation product of parathyroid messenger RNA. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3731–3735. doi: 10.1073/pnas.71.9.3731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koj A., McFarlane A. S. Effect of endotoxin on plasma albumin and fibrinogen synthesis rates in rabbits as measured by the [14C] carbonate method. Biochem J. 1968 Jun;108(1):137–146. doi: 10.1042/bj1080137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  24. MARSH J. B., DRABKIN D. L. Metabolic channeling in experimental nephrosis. IV. Net synthesis of plasma albumin by liver slices from normal and nephrotic rats. J Biol Chem. 1958 Feb;230(2):1073–1081. [PubMed] [Google Scholar]
  25. Majumdar C., Tsukada K., Lieberman I. Liver protein synthesis after partial hepatectomy and acute stress. J Biol Chem. 1967 Feb 25;242(4):700–704. [PubMed] [Google Scholar]
  26. Mariani G., Bianchi R., Pilo A., Palla R., Toni M. G., Fusani L. Albumin catabolism measurement by a double tracer technique in uraemic patients during a single dialytic treatment. Eur J Clin Invest. 1974 Dec 5;4(6):435–442. [PubMed] [Google Scholar]
  27. Marsh J. B., Drabkin D. L., Braun G. A., Parks J. S. Factors in the stimulation of protein synthesis by subcellular preparations from rat liver. J Biol Chem. 1966 Sep 25;241(18):4168–4174. [PubMed] [Google Scholar]
  28. McCormick G. J., Shear L., Barry K. G. Alteration of hepatic protein synthesis in acute uremia. Proc Soc Exp Biol Med. 1966 May;122(1):99–102. doi: 10.3181/00379727-122-31062. [DOI] [PubMed] [Google Scholar]
  29. Milstein C., Brownlee G. G., Harrison T. M., Mathews M. B. A possible precursor of immunoglobulin light chains. Nat New Biol. 1972 Sep 27;239(91):117–120. doi: 10.1038/newbio239117a0. [DOI] [PubMed] [Google Scholar]
  30. Neuhaus O. W., Balegno H. F., Chandler A. M. Induction of plasma protein synthesis in response to trauma. Am J Physiol. 1966 Jul;211(1):151–156. doi: 10.1152/ajplegacy.1966.211.1.151. [DOI] [PubMed] [Google Scholar]
  31. Palacios R., Palmiter R. D., Schimke R. T. Identification and isolation of ovalbumin-synthesizing polysomes. I. Specific binding of 125 I-anti-ovalbumin to polysomes. J Biol Chem. 1972 Apr 25;247(8):2316–2321. [PubMed] [Google Scholar]
  32. Redman C. M., Banerjee D., Howell K., Palade G. E. Colchicine inhibition of plasma protein release from rat hepatocytes. J Cell Biol. 1975 Jul;66(1):42–59. doi: 10.1083/jcb.66.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rothschild M. A., Oratz M., Mongelli J., Fishman L., Schreiber S. S. Amino acid regulation of albumin synthesis. J Nutr. 1969 Aug;98(4):395–403. doi: 10.1093/jn/98.4.395. [DOI] [PubMed] [Google Scholar]
  34. Rothschild M. A., Oratz M., Mongelli J., Schreiber S. S. Alcohol-induced depression of albumin synthesis: reversal by tryptophan. J Clin Invest. 1971 Sep;50(9):1812–1818. doi: 10.1172/JCI106672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rothschild M. A., Oratz M., Schreiber S. S. Alcohol, amino acids, and albumin synthesis. Gastroenterology. 1974 Dec;67(6):1200–1213. [PubMed] [Google Scholar]
  36. Rothschild M. A., Oratz M., Schreiber S. S. Effects of carbon tetrachloride on albumin synthesis. J Clin Invest. 1972 Sep;51(9):2310–2314. doi: 10.1172/JCI107041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shafritz D. A., Anderson W. F. Isolation and partial characterization of reticulocyte factors M1 and M2. J Biol Chem. 1970 Nov 10;245(21):5553–5559. [PubMed] [Google Scholar]
  38. Shafritz D. A. Evidence for nontranslated messenger fibonucleic acid in membrane-bound and free polysomes of rabbit liver. J Biol Chem. 1974 Jan 10;249(1):89–93. [PubMed] [Google Scholar]
  39. Shear L. Internal redistribution of tissue protein synthesis in uremia. J Clin Invest. 1969 Jul;48(7):1252–1257. doi: 10.1172/JCI106090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sidransky H., Sarma D. S., Bongiorno M., Verney E. Effect of dietary tryptophan on hepatic polyribosomes and protein synthesis in fasted mice. J Biol Chem. 1968 Mar 25;243(6):1123–1132. [PubMed] [Google Scholar]
  41. Strober W., Mogielnicki R. P., Waldmann T. A. The role of the kidney in the metabolism of serum proteins. Ciba Found Symp. 1972;9:25–45. doi: 10.1002/9780470719923.ch3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES