Skip to main content
SpringerLink
Log in

A Pivotal Role of the Human Kidney in Catabolism of HDL Protein Components Apolipoprotein A-I and A-IV but not of A-II

  • Communication
  • Published:
Lipids

Abstract

Renal handling of major HDL components was studied by analyzing urine from patients with Fanconi syndrome, a rare renal proximal tubular reabsorption failure, including dysfunction of the kidney HDL receptor, cubilin. A high urinary excretion of apolipoprotein A-I and A-IV corresponding to a major part of the metabolism of these proteins was measured. In contrast, no urinary excretion of apolipoprotein A-II which is more hydrophobic and tighter bound to HDL was found. Control urines displayed absence of the three apolipoproteins. Urinary excretion of phospholipids, triglycerides, cholesterol and cholesterol esters in patients was as low as in controls. In conclusion, these data indicate that the human kidney is a major site for filtered nascent apolipoprotein A-I and A-IV but not for HDL particles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

apoA-I:

Apolipoprotein A-I

apoA-II:

Apolipoprotein A-II

apoA-IV:

Apolipoprotein A-IV

HDL:

High-density lipoprotein

References

  1. Srivastava RA, Srivastava N (2000) High density lipoprotein, apolipoprotein A-I, and coronary artery disease. Mol Cell Biochem 209(1–2):131–144

    Article  PubMed  CAS  Google Scholar 

  2. Graversen JH, Laurberg JM, Andersen MH, Falk E, Nieland J, Christensen J, Etzerodt M, Thogersen HC, Moestrup SK (2008) Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties. J Cardiovasc Pharmacol 51(2):170–177

    PubMed  CAS  Google Scholar 

  3. Newton RS, Krause BR (2002) HDL therapy for the acute treatment of atherosclerosis. Atheroscler Suppl 3(4):31–38

    Article  PubMed  CAS  Google Scholar 

  4. Nicholls SJ, Tuzcu EM, Sipahi I, Schoenhagen P, Crowe T, Kapadia S, Nissen SE (2006) Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J Am Coll Cardiol 47(5):992–997

    Article  PubMed  CAS  Google Scholar 

  5. Singh IM, Shishehbor MH, Ansell BJ (2007) High-density lipoprotein as a therapeutic target: a systematic review. JAMA 298(7):786–798

    Article  PubMed  CAS  Google Scholar 

  6. von Eckardstein A, Nofer JR, Assmann G (2001) High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 21(1):13–27

    Google Scholar 

  7. Marsh JB, Welty FK, Schaefer EJ (2000) Stable isotope turnover of apolipoproteins of high-density lipoproteins in humans. Curr Opin Lipidol 11(3):261–266

    Article  PubMed  CAS  Google Scholar 

  8. Spady DK, Woollett LA, Meidell RS, Hobbs HH (1998) Kinetic characteristics and regulation of HDL cholesteryl ester and apolipoprotein transport in the apoA-I-/- mouse. J Lipid Res 39(7):1483–1492

    PubMed  CAS  Google Scholar 

  9. Wang N, Arai T, Ji Y, Rinninger F, Tall AR (1998) Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice. J Biol Chem 273(49):32920–32926

    Article  PubMed  CAS  Google Scholar 

  10. Woollett LA, Spady DK (1997) Kinetic parameters for high density lipoprotein apoprotein AI and cholesteryl ester transport in the hamster. J Clin Invest 99(7):1704–1713

    Article  PubMed  CAS  Google Scholar 

  11. Glass CK, Pittman RC, Keller GA, Steinberg D (1983) Tissue sites of degradation of apoprotein A-I in the rat. J Biol Chem 258(11):7161–7167

    PubMed  CAS  Google Scholar 

  12. Braschi S, Neville TA, Maugeais C, Ramsamy TA, Seymour R, Sparks DL (2000) Role of the kidney in regulating the metabolism of HDL in rabbits: evidence that iodination alters the catabolism of apolipoprotein A-I by the kidney. Biochemistry 39(18):5441–5449

    Article  PubMed  CAS  Google Scholar 

  13. Lee JY, Lanningham-Foster L, Boudyguina EY, Smith TL, Young ER, Colvin PL, Thomas MJ, Parks JS (2004) Prebeta high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice. J Lipid Res 45(4):716–728

    Article  PubMed  CAS  Google Scholar 

  14. Lee JY, Parks JS (2005) ATP-binding cassette transporter AI and its role in HDL formation. Curr Opin Lipidol 16(1):19–25

    Article  PubMed  Google Scholar 

  15. Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, Christensen EI, Aminoff M, de la Chapelle A, Krahe R et al (1999) The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. Nat Med 5(6):656–661

    Article  PubMed  CAS  Google Scholar 

  16. Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW, Thakker RV, Unwin RJ, Wrong O (2001) Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int 60(5):1885–1892

    Article  PubMed  CAS  Google Scholar 

  17. Castro GR, Fielding CJ (1988) Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry 27(1):25–29

    Article  PubMed  CAS  Google Scholar 

  18. Bartlett GR (1959) Phosphorus assay in column chromatography. J Biol Chem 234(3):466–468

    PubMed  CAS  Google Scholar 

  19. Bhandaru RR, Srinivasan SR, Pargaonkar PS, Berenson GS (1977) A simplified colorimetric micromethod for determination of serum cholesterol. Lipids 12(12):1078–1080

    Article  PubMed  CAS  Google Scholar 

  20. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917

    PubMed  CAS  Google Scholar 

  21. Christensen EI, Nielsen S, Moestrup SK, Borre C, Maunsbach AB, de Heer E, Ronco P, Hammond TG, Verroust P (1995) Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules. Eur J Cell Biol 66(4):349–364

    PubMed  CAS  Google Scholar 

  22. Lingenhel A, Lhotta K, Neyer U, Heid IM, Rantner B, Kronenberg MF, Konig P, von Eckardstein A, Schober M, Dieplinger H et al (2006) Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the type of proteinuria. J Lipid Res 47(9):2071–2079

    Article  PubMed  CAS  Google Scholar 

  23. Seishima M, Muto Y (1987) An increased apo A-IV serum concentration of patients with chronic renal failure on hemodialysis. Clin Chim Acta 167(3):303–311

    Article  PubMed  CAS  Google Scholar 

  24. Cutillas PR, Chalkley RJ, Hansen KC, Cramer R, Norden AG, Waterfield MD, Burlingame AL, Unwin RJ (2004) The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells. Am J Physiol Renal Physiol 287(3):F353–F364

    Article  PubMed  CAS  Google Scholar 

  25. van’t Hoff WG (1996) Biology and genetics of inherited renal tubular disorders. Exp Nephrol 4(5):253–262

    PubMed  CAS  Google Scholar 

  26. Ooi EM, Watts GF, Farvid MS, Chan DC, Allen MC, Zilko SR, Barrett PH (2005) High-density lipoprotein apolipoprotein A-I kinetics in obesity. Obes Res 13(6):1008–1016

    Article  PubMed  CAS  Google Scholar 

  27. Li L, Chen J, Mishra VK, Kurtz JA, Cao D, Klon AE, Harvey SC, Anantharamaiah GM, Segrest JP (2004) Double belt structure of discoidal high density lipoproteins: molecular basis for size heterogeneity. J Mol Biol 343(5):1293–1311

    Article  PubMed  CAS  Google Scholar 

  28. Martin DD, Budamagunta MS, Ryan RO, Voss JC, Oda MN (2006) Apolipoprotein A-I assumes a “looped belt” conformation on reconstituted high density lipoprotein. J Biol Chem 281(29):20418–20426

    Article  PubMed  CAS  Google Scholar 

  29. Lee JY, Timmins JM, Mulya A, Smith TL, Zhu Y, Rubin EM, Chisholm JW, Colvin PL, Parks JS (2005) HDLs in apoA-I transgenic Abca1 knockout mice are remodeled normally in plasma but are hypercatabolized by the kidney. J Lipid Res 46(10):2233–2245

    Article  PubMed  CAS  Google Scholar 

  30. Oram JF (2000) Tangier disease and ABCA1. Biochim Biophys Acta 1529(1–3):321–330

    PubMed  CAS  Google Scholar 

  31. Timmins JM, Lee JY, Boudyguina E, Kluckman KD, Brunham LR, Mulya A, Gebre AK, Coutinho JM, Colvin PL, Smith TL et al (2005) Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 115(5):1333–1342

    PubMed  CAS  Google Scholar 

  32. Mekki K, Bouchenak M, Remaoun M, Belleville JL (2004) Effect of long-term hemodialysis on plasma lecithin: cholesterol acyltransferase activity and the amounts and compositions of HDL2 and HDL3 in hemodialysis-treated patients with chronic renal failure: a 9-year longitudinal study. Med Sci Monit 10(8):CR439–CR446

    PubMed  CAS  Google Scholar 

  33. Duval F, Frommherz K, Atger V, Drueke T, Lacour B (1989) Influence of end-stage renal failure on concentrations of free apolipoprotein A-1 in serum. Clin Chem 35(6):963–966

    PubMed  CAS  Google Scholar 

  34. Julve J, Escola-Gil JC, Ribas V, Gonzalez-Sastre F, Ordonez-Llanos J, Sanchez-Quesada JL, Blanco-Vaca F (2002) Mechanisms of HDL deficiency in mice overexpressing human apoA-II. J Lipid Res 43(10):1734–1742

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by The Danish Medical Research Council.

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, University of Aarhus, 8000, Aarhus C, Denmark

    Jonas Heilskov Graversen, Henning Nielsen & Søren Kragh Moestrup

  2. Department of Cell biology, University of Aarhus, 8000, Aarhus C, Denmark

    Erik Ilsø Christensen

  3. Institut Pasteur, INSERM U545, Lille, France

    Graciela Castro & Abdelmejid Kandoussi

  4. Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge, UK

    Anthony Norden

  5. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

    Søren Kragh Moestrup

Authors
  1. Jonas Heilskov Graversen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Graciela Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdelmejid Kandoussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henning Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erik Ilsø Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anthony Norden
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Søren Kragh Moestrup
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonas Heilskov Graversen.

Additional information

Abdelmejid Kandoussi: Deceased.

About this article

Cite this article

Graversen, J.H., Castro, G., Kandoussi, A. et al. A Pivotal Role of the Human Kidney in Catabolism of HDL Protein Components Apolipoprotein A-I and A-IV but not of A-II. Lipids 43, 467–470 (2008). https://doi.org/10.1007/s11745-008-3169-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-008-3169-2

Keywords

Search

Navigation