Determination of dideoxyosone precursors of AGEs in human lens proteins

Linetsky M, Johar SK, Meltretter J, Padmanabha S, Parmar T, Vasavada AR, Pischetsrieder M, Nagaraj RH (2011)

Publication Type: Journal article

Publication year: 2011

Journal

Archives of Biochemistry and Biophysics Elsevier

Publisher: Elsevier

Book Volume: 514

Pages Range: 16-26

DOI: 10.1016/j.abb.2011.07.012

Abstract

Dideoxyosones (DDOs) are intermediates in the synthesis of advanced glycation endproducts (AGEs), such as pentosidine and glucosepane. Although the formation of pentosidine and glucosepane in the human lens has been firmly established, the formation of DDOs has not been demonstrated. The aim of this study was to develop a reliable method to detect DDOs in lens proteins. A specific DDO trapping agent, biotinyl-diaminobenzene (3,4-diamino-N-(3-[5-(2- oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]aminopropyl)benzamide) (BDAB) was added during in vitro protein glycation or during protein extraction from human lenses. In vitro glycated human lens protein showed strong reaction in monomeric and polymeric crosslinked proteins by Western blot and ELISA. Glycation of BSA in the presence of BDAB resulted in covalent binding of BDAB to the protein and inhibited pentosidine formation. Mass spectrometric analysis of lysozyme glycated in the presence of BDAB showed the presence of quinoxalines at lysine residues at positions K1, K33, K96, and K116. The ELISA results indicated that cataractous lens proteins contain significantly higher levels of DDO than non-cataractous lenses (101.9 ± 67.8 vs. 31.7 ± 19.5 AU/mg protein, p < 0.0001). This study provides first direct evidence of DDO presence in human tissue proteins and establishes that AGE crosslink synthesis in the human lens occurs via DDO intermediates. © 2011 Elsevier Inc. All rights reserved.

Authors with CRIS profile

Jasmin Meltretter Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl) Monika Pischetsrieder Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

Involved external institutions

Case Western Reserve University US United States (USA) (US) Iladevi Cataract and IOL Research Center IN India (IN)

How to cite

APA:

Linetsky, M., Johar, S.K., Meltretter, J., Padmanabha, S., Parmar, T., Vasavada, A.R.,... Nagaraj, R.H. (2011). Determination of dideoxyosone precursors of AGEs in human lens proteins. Archives of Biochemistry and Biophysics, 514, 16-26. https://doi.org/10.1016/j.abb.2011.07.012

MLA:

Linetsky, Mikhail, et al. "Determination of dideoxyosone precursors of AGEs in human lens proteins." Archives of Biochemistry and Biophysics 514 (2011): 16-26.

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