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. 1974 Feb;53(2):403–407. doi: 10.1172/JCI107573

Biochemical properties of human glomerular basement membrane in normal and diabetic kidneys.

N A Kefalides 1
PMCID: PMC301482  PMID: 11344553

Abstract

To determine the presence of any significant structural abnormalities in the glomerular basement membrane (GBM) of diabetic individuals, GBM from normal and diabetic human kidneys were isolated and analyzed chemically and structurally. The amino acid composition of the normal GBM revealed the presence of significant amounts of hydroxyproline, hydroxylysine, glycine, and carbohydrate suggesting the presence of a collagen-like protein. There was no significant increase in the amount of hydroxylysine, hydroxyproline, or in the hydroxylysine-linked glycoside glucosyl-galactose in the diabetic kidneys. There was, however, a significant decrease in the cystine and sialic acid content of GBM from diabetic kidneys. It was further shown that the alpha-chains isolated from the collagens of normal and diabetic basement membranes had similar amino acid and carbohydrate compositions. The hydroxylysine, hydroxyproline, glycine, and hexose contents were higher by 82, 56, 74, and 94%, respectively in the alpha-chains compared with the intact basement membranes from both the normal and diabetic kidneys. The results indicate that the slight increases in hydroxylysine and hexose content observed occasionally in diabetic GBM preparations are of no statistical significance and cannot be attributed to increases in the activities of enzymes which hydroxylate lysine or glycosylate hydroxylysine, respectively.

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Selected References

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

  1. BERGSTRAND A., BUCHT H. Electron microscopic investigations on the glomerular lesions in diabetes mellitus (diabetic glomerulosclerosis). Lab Invest. 1957 Jul-Aug;6(4):293–300. [PubMed] [Google Scholar]
  2. BLOODWORTH J. M., Jr Diabetic microangiopathy. Diabetes. 1963 Mar-Apr;12:99–114. doi: 10.2337/diab.12.2.99. [DOI] [PubMed] [Google Scholar]
  3. BURSTEIN R., SOULE S. D., BLUMENTHAL H. T. Histogenesis of pathological processes in placentas of metabolic disease in pregnancy. II. The diabetic state. Am J Obstet Gynecol. 1957 Jul;74(1):96–104. doi: 10.1016/s0002-9378(16)37007-7. [DOI] [PubMed] [Google Scholar]
  4. Beisswenger P. G., Spiro R. G. Human glomerular basement membrane: chemical alteration in diabetes mellitus. Science. 1970 May 1;168(3931):596–598. doi: 10.1126/science.168.3931.596. [DOI] [PubMed] [Google Scholar]
  5. Beisswenger P. J., Spiro R. G. Studies on the human glomerular basement membrane. Composition, nature of the carbohydrate units and chemical changes in diabetes mellitus. Diabetes. 1973 Mar;22(3):180–193. doi: 10.2337/diab.22.3.180. [DOI] [PubMed] [Google Scholar]
  6. Bellamy G., Bornstein P. Evidence for procollagen, a biosynthetic precursors of collagen. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1138–1142. doi: 10.1073/pnas.68.6.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Denduchis B., Kefalides N. A., Bezkorovainy A. The chemistry of sheep anterior lens capsule. Arch Biochem Biophys. 1970 Jun;138(2):582–589. doi: 10.1016/0003-9861(70)90384-x. [DOI] [PubMed] [Google Scholar]
  8. Denduchis B., Kefalides N. A. Immunochemistry of sheep anterior lens capsule. Biochim Biophys Acta. 1970 Nov 17;221(2):357–366. doi: 10.1016/0005-2795(70)90276-x. [DOI] [PubMed] [Google Scholar]
  9. FARQUHAR M. G., HOPPER J., Jr, MOON H. D. Diabetic glomerulosclerosis: electron and light microscopic studies. Am J Pathol. 1959 Jul-Aug;35(4):721–753. [PMC free article] [PubMed] [Google Scholar]
  10. GOLDENBERG S., ALEX M., JOSHI R. A., BLUMENTHAL H. T. Nonatheromatous peripheral vascular disease of the lower extremity in diabetes mellitus. Diabetes. 1959 Jul-Aug;8(4):261–273. doi: 10.2337/diab.8.4.261. [DOI] [PubMed] [Google Scholar]
  11. Grant M. E., Kefalides N. A., Prockop D. J. The biosynthesis of basement membrane collagen in embryonic chick lens. I. Delay between the synthesis of polypeptide chains and the secretion of collagen by matrix-free cells. J Biol Chem. 1972 Jun 10;247(11):3539–3544. [PubMed] [Google Scholar]
  12. Grant M. E., Kefalides N. A., Prockop D. J. The biosynthesis of basement membrane collagen in embryonic chick lens. II. Synthesis of a precursor form by matrix-free cells and a time-dependent conversion to chains in intact lens. J Biol Chem. 1972 Jun 10;247(11):3545–3551. [PubMed] [Google Scholar]
  13. KIMMELSTIEL P., KIM O. J., BERES J. Studies on renal biopsy specimens, with the aid of the electron microscope. I. Glomeruli in diabetes. Am J Clin Pathol. 1962 Sep;38:270–279. doi: 10.1093/ajcp/38.3.270. [DOI] [PubMed] [Google Scholar]
  14. KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
  15. Kefalides N. A., Denduchis B. Structural components of epithelial and endothelial basement membranes. Biochemistry. 1969 Nov;8(11):4613–4621. doi: 10.1021/bi00839a057. [DOI] [PubMed] [Google Scholar]
  16. Kefalides N. A., Forsell-Knott L. Structural changes in the protein and carbohydrate components of glomerular basement membrane in aminonucleoside nephrosis. Biochim Biophys Acta. 1970 Mar 17;203(1):62–66. doi: 10.1016/0005-2736(70)90035-0. [DOI] [PubMed] [Google Scholar]
  17. Kefalides N. A. Isolation and characterization of cyanogen bromide peptides from basement membrane collagen. Biochem Biophys Res Commun. 1972 Jun 9;47(5):1151–1158. doi: 10.1016/0006-291x(72)90955-2. [DOI] [PubMed] [Google Scholar]
  18. Kefalides N. A. Isolation and characterization of the collagen from glomerular basement membrane. Biochemistry. 1968 Sep;7(9):3103–3112. doi: 10.1021/bi00849a012. [DOI] [PubMed] [Google Scholar]
  19. Kefalides N. A. Isolation of a collagen from basement membranes containing three identical - chains. Biochem Biophys Res Commun. 1971 Oct 1;45(1):226–234. doi: 10.1016/0006-291x(71)90073-8. [DOI] [PubMed] [Google Scholar]
  20. MOORE S., STEIN W. H. A modified ninhydrin reagent for the photometric determination of amino acids and related compounds. J Biol Chem. 1954 Dec;211(2):907–913. [PubMed] [Google Scholar]
  21. Miller E. J. Isolation and characterization of a collagen from chick cartilage containing three identical alpha chains. Biochemistry. 1971 Apr 27;10(9):1652–1659. doi: 10.1021/bi00785a024. [DOI] [PubMed] [Google Scholar]
  22. Siperstein M. D., Unger R. H., Madison L. L. Studies of muscle capillary basement membranes in normal subjects, diabetic, and prediabetic patients. J Clin Invest. 1968 Sep;47(9):1973–1999. doi: 10.1172/JCI105886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spiro R. G. Studies on the renal glomerular basement membrane. Nature of the carbohydrate units and their attachment to the peptide portion. J Biol Chem. 1967 Apr 25;242(8):1923–1932. [PubMed] [Google Scholar]
  24. WEIMER H. E., MOSHIN J. R. Serum glyco protein concentrations in experimental tuberculosis of guinea pigs. Am Rev Tuberc. 1953 Oct;68(4):594–602. doi: 10.1164/art.1953.68.4.594. [DOI] [PubMed] [Google Scholar]
  25. Westberg N. G., Michael A. F. Human glomerular basement membrane: chemical composition in diabetes mellitus. Acta Med Scand. 1973 Jul-Aug;1-2(1):39–47. doi: 10.1111/j.0954-6820.1973.tb19411.x. [DOI] [PubMed] [Google Scholar]

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