Volume 11 Supplement 2

17th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Uremic albumin blocks reverse cholesterol transfer: role of lysine modifications

  • Veronika Binder1,
  • Michael Holzer1,
  • Dalia El-Gamal1,
  • Sabine Dirnberger1 and
  • Gunther Marsche1Email author
BMC Pharmacology201111(Suppl 2):A32

https://doi.org/10.1186/1471-2210-11-S2-A32

Published: 5 September 2011

Background

Due to a lack of antioxidant enzymes in plasma, plasma proteins are preferential targets of oxidant injury. Reaction of chlorinated oxidants (e.g. hypochlorous acid), generated from activated neutrophils, with plasma albumin gives rise to formation of an oxidized protein fraction, termed advanced oxidation protein products (AOPPs). AOPP-albumin is a potent high-density lipoprotein (HDL) receptor antagonist, blocking HDL association and reverse cholesterol transport (RCT). However, it is not known whether structural alterations and/or an increase in negative charge (through oxidation of positively charged lysine residues on albumin) are required for high affinity binding to SR-BI.

Methods and results

T-lymphocytes were incubated with AF 488-TFP-labelled HDL in the presence of different AOPP-albumin preparations (albumin oxidized in vitro by the myeloperoxidase product hypochlorous acid). HDL association to SR-BI was measured by flow cytometry. Our data show that already mild oxidation of albumin generates a high affinity ligand to SR-BI that effectively displaces HDL from the receptor. Oxidation/decomposition of lysine residues are required for binding of AOPP-albumin to SR-BI since masking lysine residues prior to oxidation as well as regeneration of lysine oxidation products completely averted binding. Interestingly, modification of albumin-located lysine residues with reactive carbonyls only moderately increased binding affinity of albumin to SR-BI.

Conclusions

Structural alterations induced by lysine oxidation rather than an increased negative charge determine binding affinity of AOPP-albumin to SR-BI.

Declarations

Acknowledgements

This work was supported by the FWF grants (P21004-B02, P22521-B18 and P22976-B18), and the PhD Program MOLMED of the Medical University of Graz.

Authors’ Affiliations

(1)
Institute of Experimental and Clinical Pharmacology, Medical University of Graz

Copyright

© Binder et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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